Notice: The following Research Articles on Ionic Calcium & Diseases are Shared Here for Your Convenience and Information Only. The Same Articles Can Be Found Through Internet Searches Such As from Pub Med or NIH websites. ACRI Is Not Directly Involved in This Research and Are Not Making Any Claims.
Oncology
AKT activation enhances resistance to apoptosis and induces cell survival signaling through multiple downstream pathways. We now present evidence that AKT is activated in HTLV-1-transformed cells and that Tax activation ofAKT is linked to NF-jB activation.
Fifteen human placentas were obtained at term. Placental fragments were incubated in a bicarbonate-buffered Earle's solution. Additions of glutamate (1 mM) or glutamine (1 or 2 mM) were made. All incubations showed a net utilization of glucose.
The development of malignant tumors results from deregulated proliferation or an inability of cells to undergo apoptotic cell death. Experimental works of the past decade have highlighted the importance of calcium (Ca2 þ ) in the regulation of apoptosis.
Electroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment. Electroporation with calcium causes ATP (adenosine triphosphate) depletion and cancer cell death and could be a novel cancer treatment.
High calcium consumption may confer a reduced risk of colorectal cancer. Dai and colleagues recently reported in a case-control study that intake of calcium may be associated with a decreased risk of colorectal adenoma only when the dietary calcium:magnesium intake ratio is low.
Calcineurin (PP2B), a serine threonine kinase controlled by cellular calcium, was originally identified by Klee and colleagues in extracts of mammalian brain. Within the past few years this phosphatase has been implicated in a wide variety of biological responses including lymphocyte activation, neuronal and muscle development, axonal pathfinding and morphogenesis of vertebrate heart valves.
This study aimed to evaluate a complex association between dietary vitamin D, calcium, and retinol intake and pancreatic cancer risk. Methods Pancreatic cancer cases (n = 532) diagnosed in 1995–1999 were identified using rapid case ascertainment methods and were frequently matched to population-based controls (n = 1,701) in the San Francisco Bay Area.
A high calcium intake, mainly from dairy products, may increase prostate cancer risk by lowering concentrations of 1,25-dihydroxyvitamin, a hormone thought to protect against prostate cancer. The results of epidemiologic studies of this hypothesis are inconclusive.
Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors.
Electroporation of cells with short, high-voltage pulses causes a transient permeabilization of cell membranes that permits passage of otherwise nonpermeating ions and molecules. In this study, we illustrate how electroporation with isotonic calcium can achieve highly effective cancer cell kill in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis.
The calcium signal is implicated in a variety of processes important in tumor progression (e.g. proliferation and invasiveness). The calcium signal has also been shown to be important in other processes important in cancer progression including the development of resistance to current cancer therapies. In this review, we discuss how Ca2+ channels, pumps and exchangers may be drug targets in some cancer types.
Senescence is one of the primary responses to the activation of oncoproteins or down-regulation of tumor suppressors in normal cells and is therefore considered as being anti-tumorigenic but the mechanisms controlling this process are still much unknown. Calcium (Ca2+) plays a major role in many cellular processes and calcium channels control many of the “hallmarks of cancer” but their involvement in tumor initiation is poorly understood and remains unclear.
The mitochondrial calcium uniporter is an evolutionarily conserved calcium channel, and its biophysical properties and relevance to cell death, bioenergetics and signalling have been investigated for decades. However, the genes encoding this channel have only recently been discovered, opening up a new ‘molecular era’ in the study of its biology. We now know that the uniporter is not a single protein but rather a macromolecular complex consisting of pore-forming and regulatory subunits.
Lung cancer is the most common malignant tumor in the world. Calcium is a ubiquitous cellular signal, which is crucial in cancer. This review presents regulation of calcium signaling in lung cancer. Altered expression of specific Ca2+ channels and Ca2+-binding proteins are characterizing features of lung cancer, which regulate cell signaling pathway leading to cell proliferation or apoptosis. Chemoresistance is frequent in lung cancer.
Killing cancer cells by cytotoxic T lymphocytes (CTL) and by natural killer (NK) cells is of vital importance. Cancer cell proliferation and apoptosis depend on the intracellular Ca2+ concentration, and the expression of numerous ion channels with the ability to control intracellular Ca2+ concentrations has been correlated with cancer.
The common preference of cancers for lactic acid-generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers can escape immune destruction by suppressing the anti-cancer immune response through maintaining a relatively low pH in their micro-environment.
We investigated in this study the contributions of S100B and calcium-dependent PKC (cPKC) signalling pathways to the activation of wild-type p53. We first confirmed that S100B expression in mouse embryo fibroblasts enhanced specific nuclear accumulation of wild-type p53. We next demonstrated that wild-type p53 nuclear translocation and accumulation is dependent on cPKC activity.
Increased cancer risk is associated with select dietary factors. Dietary lifestyles can alter systemic acid-base balance over time. Acidogenic diets, which are typically high in animal protein and salt and low in fruits and vegetables, can lead to a sub-clinical or low-grade state of metabolic acidosis. The relationship between diet and cancer risk prompts questions about the role of acidosis in the initiation and progression of cancer.
DNA repair ability is reduced in a variety of pathologic conditions. In addition, in some of these diseases a disturbance in cellular Ca homeostasis occurs or cytosolic [Ca 2+] responses to various stimuli are impaired. The leading environmental cause for genomal DNA damage is ultraviolet (UV) irradiation. The aims of the present study were (I) to evaluate a possible dependence of UV-induced DNA repair ability on cytosolic Ca 2+ in human lymphocytes and (2) to assess the direct effect of UV irradiation on Ca 2+ homeostasis in these cells.
Human papillomaviruses (HPVs) are associated with the majority of cervical cancers and encode a transforming protein, E6, that interacts with the tumor suppressor protein p53. Because E6 has p53-independent transforming activity, the yeast two-hybrid system was used to search for other E6-binding proteins. One such protein, E6BP, interacted with cancer-associated HPV E6 and with bovine papillomavirus type 1 (BPV-1) E6. The transforming activity of BPV-1 E6 mutants correlated with their E6BP-binding ability.
XRCC4 is a non-homologous end-joining protein employed in DNA double-strand break repair and in V(D)J recombination. In mice, XRCC4-deficiency causes a pleiotropic phenotype, which includes embryonic lethality and massive neuronal apoptosis. When DNA damage is not repaired, activating the cell cycle checkpoint protein p53 can lead to apoptosis. Here, we show that p53-de®ciency rescues several aspects of the XRCC4-deficient phenotype, including embryonic lethality, neuronal apoptosis, and impaired cellular proliferation.
Here we report a flexible amperometric lactate biosensor using silver nanoparticle based conductive electrode. Mechanically bendable cross-serpentine-shaped silver electrode is generated on flexible substrate for the mechanical durability such as bending. The biosensor is designed and fabricated by modifying silver electrode with lactate oxidase immobilized by bovine serum albumin.
Cellular stresses, such as growth factor deprivation, DNA damage or oncogene expression, lead to stabilization and activation of the p53 tumour suppressor protein. Depending on the cellular context, this results in one of two different outcomes: cell cycle arrest or apoptotic cell death. Cell death induced through the p53 pathway is executed by the caspase proteinases, which, by cleaving their substrates, lead to the characteristic
Human cells lacking functional p53 exhibit a partial deficiency in nucleotide excision repair (NER), the pathway for repair of UV-induced DNA damage. The global genomic repair (GGR) subpathway of NER, but not transcription-coupled repair (TCR), is mainly affected by p53 loss or inactivation. We have utilized mouse embryo fibroblasts (MEFs) lacking p53 genes or downstream effector genes of the p53 pathway, gadd45 (Gadd45a) or p21 (Cdkn1a), as well as MEFs lacking both gadd45 and p21 genes to address the potential contribution of these downstream effectors to p53-associated DNA repair.
Many cellular stimuli result in the induction of both the tumor suppressor p53 and NF-kB. In contrast to activation of p53, which is associated with the induction of apoptosis, stimulation of NF-kB has been shown to promote resistance to programmed cell death. These observations suggest that a regulatory mechanism must exist to integrate these opposing outcomes and coordinate this critical cellular decision-making event.
The tumor suppressor p53 is a key protein in preventing cell transformation and tumor progression. Activated by a variety of stimuli, p53 regulates cell-cycle arrest and apoptosis. Along with its well-documented transcriptional control over cell-death programs within the nucleus, p53 exerts crucial although still poorly understood functions in the cytoplasm, directly modulating the apoptotic response at the mitochondrial level.
p53 plays an essential part in the maintenance of the cellular genetic stability after a DNA-damaging event such as ultraviolet (UV) radiation. Following UV radiation, the amount of p53 protein is elevated. The increased p53 is believed to induce cell cycle arrest, promote nucleotide excision repair (NER) and apoptosis. To study if cells respond differently to high- and low-dose UV radiation, we examined the DNA repair efficiency and apoptosis rate of human and murine fibroblasts after UV radiation.
The p53 tumour suppressor protein is a highly potent transcription factor which, under normal circumstances, is maintained at low levels through the action of MDM2, an E3 ubiquitin ligase which directs p53 ubiquitylation and degradation. Expression of the mdm2 gene is stimulated by p53 and this reciprocal relationship forms the basis of a negative feedback loop. Both genotoxic and non-genotoxic stresses that induce p53 focus principally on interruption of the p53-MDM2 loop with the consequence that p53 becomes stabilized, leading to changes in the expression of p53-responsive genes.
Activation of the p53 transcription factor in response to a variety of cellular stresses, including DNA damage and oncogene activation, initiates a program of gene expression that blocks the proliferative expansion of damaged cells. While the beneficial impact of the anti-cancer function of p53 is well established, several recent papers suggest that p53 activation may in some circumstances act in a manner detrimental to the long-term homeostasis of the organism.
The phosphoinositide 3-kinase (PI3-kinase) signalling pathway plays a key role in the regulation of cell survival and proliferation. We show that the PI3-kinase/Akt pathway is constitutively active in primary acute myeloid leukaemia (AML) cells and that blockade by the selective inhibitor LY294002 reduces survival of the total blast population (mean 52%). The ERK/MAPK module is also constitutively active and treatment with the MAPKK inhibitor U0126 reduces cell survival by 22%.
Apoptosis is now recognized as an important component in many progressive and acute neurodegenerative diseases. Extracellular signals and intracellular mechanisms triggering and regulating apoptosis in neuronal cells are still a matter of investigation. Here we review data from our and other laboratories with the aim to elucidate the nature of some proteins which are known to be involved in cell cycle regulation as well as in promoting degeneration and apoptosis of neurons.
S100B protein is elevated in the brains of patients with early stages of Alzheimer’s disease and Down’s syndrome. S100A4 is correlated with the development of metastasis. Both proteins bind to p53 tumor suppressor. We found that both S100B and S100A4 bind to the tetramerization domain of p53 (residues 325–355) only when exposed in lower oligomerization states and so they disrupt the tetramerization of p53. In addition, S100B binds to the negative regulatory and nuclear localization domains, which results in a very tight binding to p53 protein sequences that exposed the tetramerization domain in their C terminus.
Calcium is an important ubiquitous second messenger regarding the maintenance of cellular homeostasis, and is therefore tightly regulated. Calcium induces cell death when internalised into cancer cells after permeabilization of the cell membrane by electroporation. It is established that radiation causes damage to the lipids and proteins of the cell membrane; and ionizing radiation also causes permeabilization of the cell membrane by peroxidation of the phosphor-lipid layer.
S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins. A consensus sequence for S100B target proteins was published as (K/R)(L/I)xWxxIL and matches a region in the actin capping protein CapZ (V.V. Ivanenkov, G.A. Jamieson, Jr., E. Gruenstein, R.V. Dimlich, Characterization of S-100b binding epitopes.
p53 has been implicated in the activation of both death-receptor and Apaf-1-dependent apoptosis. Signalling through death receptors such as tumour necrosis factor receptor (TNFR) generates both pro- and anti-apoptotic signals, and activation of NF-kB functions to protect cells from death under these circumstances. In other situations, however, NF-kB contributes to apoptosis.
The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range. Much has been learned in recent years about the diversity of signal transduction through the CaSR and the various factors that affect receptor expression.
Although the mainstay of treatment for hormone responsive breast tumors is targeted endocrine therapy, many patients develop de novo or acquired resistance and are treated with chemotherapeutic drugs. The vast majority (80%) of estrogen receptor positive tumors also express wild type p53 protein that is a major determinant of the DNA damage response.
The integration of calcium and a p53–Mdm2 oscillator model is studied using a deterministic as well as a stochastic approach, to investigate the impact of a calcium wave on single cell dynamics and on the inter-oscillator interaction. The high dose of calcium in the system activates the nitric oxide synthase, synthesizing nitric oxide which then downregulates Mdm2 and influences drastically the p53–Mdm2 network regulation, lifting the system from a normal to a stressed state.
The pathways and identification of cell injury and cell death are of key importance to the practice of diagnostic and research toxicologic pathology. Following a lethal injury, cellular reactions are initially reversible. Currently, we recognize two patterns, oncosis and apoptosis. Oncosis, derived from the Greek word "swelling," is the common pattern of change in infarcts and in zonal killing following chemical toxicity, e.g., centrilobular hepatic necrosis after CC14 toxicity.
The p53 tumour-suppressor gene is mutated in 60% of human tumours, and the product of the gene acts as a suppressor of cell division. It is thought that the growth-suppressive effects of p53 are mediated through the transcriptional transactivation activity of the protein.
Loss of p53 function occurs during the development of most, if not all, tumour types. This paves the way for genomic instability, tumour-associated changes in metabolism, insensitivity to apoptotic signals, invasiveness and motility. However, the nature of the causal link between early tumorigenic events and the induction of the p53-mediated checkpoints that constitute a barrier to tumour progression remains uncertain
Calcium is a ubiquitous second messenger that regulates many cellular functions, including cell growth, differentiation and neural signal transduction. S100A and S100B proteins are members of a growing subfamily of the EF-hand calcium binding protein superfamily, possessing ~40% sequence identity. The S100B protein is one of the ‘elite’ proteins in the field of calcium signaling, being implicated in cell cycle arrest and apoptosis1 as well as in Down’s syndrome and Alzheimer’s disease.
Osteoporosis
Calcium transport and calcium signalling mechanisms in bone cells have, in many cases, been discovered by study of diseases with disordered bone metabolism. Calcium matrix deposition is driven primarily by phosphate production, and disorders in bone deposition include abnormalities in membrane phosphate transport such as in chondrocalcinosis, and defects in phosphate-producing enzymes such as in hypophosphatasia.
Antiretroviral therapy (ART) has transformed HIV infection from a terminal disease to a manageable chronic illness. While incidence of AIDS-defining conditions has declined, other comorbidities have increased (1), including osteoporosis and fragility fractures (2-7). Both viral and host factors likely contribute to bone loss and fracture risk: HIV infection mediated by certain viral proteins, HIV-associated inflammation, lifestyle and behavioral factors, underlying genetic predisposition, comorbidities, and ART (8-14).
This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks.
Neurodegenerative Diseases
Alzheimer’s disease (AD) and aging result in impaired ability to store memories, but the cellular mechanisms responsible for these defects are poorly understood. Presenilin 1 (PS1) mutations are responsible for many early-onset familial AD (FAD) cases. The phenomenon of hippocampal long-term potentiation (LTP) is widely used in studies of memory formation and storage. Recent data revealed long-term LTP maintenance (L-LTP) is impaired in PS1-M146V knock-in (KI) FAD mice.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective and progressive loss of upper and lower motor neurons (MNs) of the brainstem, spinal cord and cerebral cortex. Key discoveries in the field of ALS have exponentially increased since it was first described in 1869 by Jean Martin Charcot, and the identification in 1993 of the first ALS-causing mutations in the gene encoding the well-studied antioxidant enzyme Cu, Zn superoxide dismutase (SOD1).
Alzheimer’s disease (AD) is the disease of lost memories. Synaptic loss is a major reason for memory defects in AD. Signaling pathways involved in memory loss in AD are under intense investigation. The role of deranged neuronal calcium (Ca2+) signaling in synaptic loss in AD is described in this review. Familial AD (FAD) mutations in presenilins are linked directly with synaptic Ca2+ signaling abnormalities, most likely by affecting endoplasmic reticulum (ER) Ca2+ leak function of presenilins.
Alzheimer’s disease (AD)-linked presenilin mutations result in pronounced endoplasmic reticulum (ER) calcium disruptions that occur prior to detectable histopathology and cognitive deficits. More subtly, these early AD-linked calcium alterations also reset neurophysiological homeostasis, such that calcium-dependent pre- and postsynaptic signaling appear functionally normal yet are actually operating under aberrant calcium signaling systems.
Trains of action potentials evoked rises in presynaptic Ca2+ concentration ([Ca2+]i) at the squid giant synapse. These increases in [Ca2+]i were spatially nonuniform during the trains, but rapidly equilibrated after the trains and slowly declined over hundreds of seconds. The trains also elicited synaptic depression and augmentation, both of which developed during stimulation and declined within a few seconds afterward.
Modeling and simulation of the calcium signaling events that precede long-term depression of synaptic activity in cerebellar Purkinje cells are performed using the Virtual Cell biological modeling framework. It is found that the unusually high density and low sensitivity of inositol-1,4,5-trisphosphate receptors (IP3R) are critical to the ability of the cell to generate and localize a calcium spike in a single dendritic spine.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by widespread inflammation, focal demyelination and a variable degree of axonal and neuronal loss. Ionic conductances regulate T cell activation as well as neuronal function and thus have been found to play a crucial role in MS pathogenesis.
Dental Health
A number of bone-filling materials containing calcium (Ca2+) and phosphate (P) ions have been used in the repair of periodontal bone defects; however, the effects that local release of Ca2+ and P ions has on biological reactions are not fully understood. In this study, we investigated the effects of various levels of Ca2+ and P ions on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells (hPDLCs).
Heart Diseases
Myocardial calcium signalling is a vital component of the normal physiological function of the heart. Key amongst the many roles calcium plays is its use as the primary signalling component of excitation–contraction coupling, the intracellular process that links cardiomyocyte depolarisation to contraction. Defective cellular calcium handling, due to abnormalities of the various components which mediate and control excitation–contraction coupling, is widely recognised as a significant patho-physiological event in the contractile dysfunction of the failing heart.
Cardiac arrhythmia, caused by disruption of the coordinated electrical activity of heart, is among the leading causes of sudden cardiac death in United States. Intracellular calcium dynamics in cardiac cells have been recognized as an important contributor in life-threatening ventricular arrhythmia (ventricular tachycardia and ventricular fibrillation) as well as increasingly prevalent atrial arrhythmias (atrial fibrillation [AF] and flutter).
Diabetes
Hyperglycemia in Diabetes Mellitus is known to have its effect on almost all body system through alterations in structural and biochemical changes in tissues.From this study it is hypothesized that alteration in calcium flux may adversely affect the insulin secretion as it is a calcium dependent process.
Infectious Diseases
Decreased bone mineral density (BMD) is prevalent in HIV-infected patients. Bisphosphonates are currently the mainstay of treatment for postmenopausal and male osteoporosis in HIV-uninfected individuals; however, their efficacy and safety in HIV-infected patients remains unclear.
Osteopenia and osteoporosis are frequent complications of HIV infection and/or its treatment. Alendronate is the only bisphosphonate approved for the treatment of osteoporosis in men and women. We conducted a 48-week prospective, randomized, openlabel study to evaluate the effects of alendronate, vitamin D, and calcium supplementation on bone mineral density (BMD) in patients with HIV infection.
Lyme borreliosis is transmitted through the bite of a tick that is infected by the bacterial spirochete Borrelia burgdorferi. Clinical manifestation of the disease can lead to heart conditions, neurological disorders, and inflammatory disorders. Oxidative stress has been implicated in the pathogenesis of many human diseases. The aim of this study was to investigate the mechanisms of oxidative stress and intracellular communication in Lyme borreliosis patients.
Epidemiological data suggest that calcium intake may influence lipid metabolism. It is unknown whether this influence also occurs in individuals with HIV/AIDS. The present study aimed to assess the relationship between dietary calcium, dairy food intake and metabolic parameters in individuals with HIV/AIDS.
It is known that exogenous RNA molecules can be taken up by eukaryotic cells and can exert a variety of biological effects both in vitro and in vivo. The modulation of human lymphocytes by exogenous RNAs has medical implications. The exogenous RNA used in this study was obtained from lymphoid organs of animals immunized with the synthetic peptide p12 of HIV-1 and was referred to as p12-RNA.
Until now, only few data have been reported on calcium levels in these patients. Generally hypocalcaemia has not been considered to be a frequent phenomenon in HIV infection and reports of reduced calcium levels in AIDS have been mostly attributed to hypoalbuminaemia or to pharmacotherapy, e.g. treatment with foscarnet or ketoconazole.
Arthritis & Stem Cells
Tumour progression is dependent on the interaction between tumour cells and cells of the surrounding microenvironment. The tumour is a dynamic milieu consisting of various cell types such as endothelial cells, fibroblasts, cells of the immune system and mesenchymal stem cells (MSCs). MSCs are multipotent stromal cells that are known to reside in various areas such as the bone marrow, fat and dental pulp.
The role of mesenchymal stem cells (MSCs) on breast cancer progression, growth and tumorigenesis remains controversial or unknown. In the present study, we investigated the role of MSCs on breast tumor induction and growth in a clinically relevant somatic breast cancer model. We first conducted in vitro studies and found that conditioned media (CM) of RCASNeu and RCAS-PyMT breast cancer cell lines and tumor cells themselves dramatically increased the proliferation and motility of MSCs and induced morphological changes of MSCs and differentiation into fibroblast-like cells.
Tumor-initiating cells are a subset of tumor cells with the ability to form new tumors; however, they account for less than 0.001% of the cells in colorectal or other types of tumors. Mesenchymal stem cells (MSCs) integrate into the colorectal tumor stroma; we investigated their involvement in tumor initiation.
It is prevalently known that tumour cells prefer inefficient cellular glycolysis, but no one has proved yet the exact reason of using ineffective cellular respiration mechanism of tumour cells. However, through our research, we have investigated that it is highly related to the lack of intracellular calcium ion because as the insufficient calcium ion causes dysfunction of mitochondria which releases reactive oxygen species (ROS), it causes mitochondrial protein mutation such as TDP-43, FUS and SOD1. Therefore, endoplasmic reticulum (ER) gets stressed and it ultimately causes alteration of RNA synthesis.
It is now widely recognised that changes of the intracellular calcium concentration have deep impact on the differentiation of various non-excitable cells including the elements of the vertebrate skeleton. It has become evident that purinergic signalling is one of the most ancient cellular mechanisms that can cause such alterations in the intracellular Ca2+-homeostasis, which are precisely set either spatially or temporally. Purinergic signalling is believed to regulate intracellular Ca2+ concentration of developing cartilage and skeletal muscle cells and suggested to play roles in the modulation of various cellular functions.
Osteoarthritis (OA) is characterised by gradual destruction of articular cartilage and leads to painful and dysfunctional knee-, hip- or hand-joints. With the increasing life expectancy and obesity, the prevalence is expected to rise. In the younger population, joint pain and disability can result from local cartilage defects resulting from injury or disease. After the introduction of autologous chondrocyte implantation (ACI) as a treatment option for localised cartilage defects in the late 80’s, cell‑based repair techniques have been extensively explored through clinical trials aiming to improve long‑term clinical outcomes.
Undifferentiated mesenchymal stem cells (MSCs) represent an important source for cell-based tissue regeneration techniques that require differentiation towards specific lineages, including chondrocytes. Chondrogenesis, the process by which committed mesenchymal cells differentiate into chondrocytes, is controlled by complex but not yet completely understood signalling mechanisms that involve many components, including intracellular signalling pathways, as well as plasma membrane receptors and ion channels.
Mitochondria play central roles in buffering intracellular Ca2+ transients. While basal mitochondrial Ca2+ (Ca2+ mito) is needed to maintain organellar physiology, Ca2+ mito overload can lead to cell death. How Ca2+ mito homeostasis is regulated is not well understood. Here we show that Miro, a known component of the mitochondrial transport machinery, regulates Drosophila neural stem cell (NSC) development through Ca2+ homeostasis control, independent of its role in mitochondrial transport.
To artificially activate embryos in somatic cell nuclear transfer (SCNT), chemical treatment with ionomycin has been used to induce transient levels of Ca²⁺ and initiate reprogramming of embryos. Ca²⁺ oscillation occurs naturally several times after fertilization (several times with 15- to 30-min intervals). This indicates how essential additional Ca²⁺ influx is for successful reprogramming of embryos. Hence, in this report, the experimental design was aimed at improving the developmental efficiency of cloned embryos by repetitive Ca²⁺ transients rather than the commonly used ionomycin treatment (4 min).
The increasing interest in stem cell research is linked to the promise of developing treatments for many lifethreatening, debilitating diseases, and for cell replacement therapies. However, performing these therapeutic innovations with safety will only be possible when an accurate knowledge about the molecular signals that promote the desired cell fate is reached.