A dysregulated calcium homeostasis as the earliest pathological sign in stem cell-derived Parkinson's disease neurons?

Parkinson’s disease(PD) is characterized by the slow and progressive demise of dopamine(DA)-synthesizing neurons in the substantia nigra pars compacta(SNc),a nucleus located in the human ventral midbrain.Neuron death also affects other regions in the brain at later stages of PD.The concomitant lack of DA in the human forebrain(striatum) leads to the typical motor symptoms of this still uncurable neurodegenerative disorder.

Transient receptor potential channels and calcium dysregulation: a pathogenic duo in Parkinson's disease

Parkinson's disease(PD) has a complex and multifactorial pathophysiology. Various studies, conducted both in pre-clinical models and PD patients, have reported a link between the disruption of calcium(Ca^(2+)) homeostasis and the subsequent development of PD. Ca^(2+) regulation is crucial for neuronal survival, differentiation,exocytosis at synapses,gene transcription,and proliferation.

NECAB family of neuronal calcium-binding proteins in health and disease

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be used to treat these disorders. We concluded that there are few clinical drugs that can improve the pathology these diseases by acting on potassium or calcium ions. Although a few novel ion-channelspecific modulators have been discovered, meaningful therapies have largely not yet been realized. The lack of target-specific drugs, their requirement to cross the blood–brain barrier, and their exact underlying mechanisms all need further attention. This review aims to explain the urgent problems that need research progress and provide comprehensive information aiming to arouse the research community's interest in the development of ion channel-targeting drugs and the identification of new therapeutic targets for that can increase the cure rate of nervous system diseases and reduce the occurrence of adverse reactions in other systems.

Copper homeostasis and neurodegenerative diseases

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Possible Mechanism of Effects of Etimicin and Gentamicin on Intracellular Calcium Homeostasis

Aim Intracellular calcium ([Ca^(2+) ]_i) is mainly regulated by mitochondriaand endo-plasmic reticula. This study was carried out to ascertain whether the elementary mechanismof the effects of etimicin (EM) and gentamicin (GM) on [Ca^(2+) ]_i is related to their effects onmitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake. Methods The effects of GMand EM on [Ca^(2+) ]_i in LLC-PK1 were determined with a fluorescent probe of Fura-2/AM. The effectsof EM and GM on mitochondrion Ca^(2+) -uptake and endoplasmic reticulum Ca^(2+) -uptake weredetermined by isotope indicator (^(45)Ca^(2+) ) . Results EM and GM at the concentration of 1mmol·L^(-1) had no significant effect on [Ca^(2+) ]_i(P. > 0.05) and at 10 mmol·L^(-1)significantly caused [Ca^(2+) ]_i to increase (P < 0.01). EM and GM at 1 mmol·L^(-1) causedmitochondrion Ca^(2+)-uptake to ascend dramatically (P < 0.05) and at 10 mmol·L^(-1) causedmitochondrion Ca^(2+) -uptake to descend significantly. EM and GM at more than 0.34 mrnol·L^(-1)significantly inhibited endoplasmic reticulum Ca^(2+) -uptake (P < 0.05 or 0.01). Conclusion Novariation of [Ca^(2+) ]_i caused by EM and GM at lower concentrations might relate to theequilibrium of their promotion of mitochondrion Ca^(2+) -uptake with their inhibition of endoplasmicreticulum Ca^(2+) -uptake. The elevation of [Ca^(2+) ]_i caused by EM and GM at higherconcentrations might correlate with their inhibition of mitochondrion Ca^(2+) -uptake andendoplasmic reticulum Ca^(2+) -uptake.

Vitamin D,calcium homeostasis and aging

Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25（OH）2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis （which remains controversial） are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance.

Fenvalerate-induced Alterations in Calcium Homeostasis in Rat Ovary

Objective To observe the effects of fenv＇,derate on calcium homeostasis in rat ovary. Methods Female SpragueDawley rats were orally given fenvalerate at dally doses of 0.00, 1.91, 9.55, and 31.80 mg/kg for four weeks. The ovary ultrastucture was observed by electron microscopy. Serum free calcium concentration was measured by atomic absorption spectrophotometry. The activities of phosphorylase a in rat ovary were evaluated by the chromatometry. The total content of calmodulin in ovary was estimated by ELISA at each stage of estrous cycle. Radioimmunoassay （R/A） was used to evaluate the level of serum progesterone. Results Histopathologically, damages of ovarian corpus luteum cells were observed. An increase in serum fi＇ee calcium concentration was observed in rats treated with 31.80mg/kg fenvalerate. The activities of phosphorylase a enhanced in all treated groups, and fenvalerate increased the total content of calmodulin significantly in estrus period. Serum progesterone levels declined in fenvalerate exposed rats in diestrus. Conclusion Fenvalerate interferes with calcium homeostasis in rat ovary. Also, the inhibitory effects of fenvalerate on serum progesterone levels may be mediated partly through calcium signals.

Mitochondrial Oxidative Stress Enhances Vasoconstriction by Altering Calcium Homeostasis in Cerebrovascular Smooth Muscle Cells under Simulated Microgravity

Objective Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts.Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process.To elucidate the mechanism for this condition,we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted(HU)rat cerebral arteries.Methods Three-week HU was used to simulate microgravity in rats.The contractile responses to vasoconstrictors,mitochondrial fission/fusion,Ca^(2+) distribution,inositol 1,4,5-trisphosphate receptor(IP3 R)abundance,and the activities of voltage-gated K+channels(KV)and Ca^(2+)-activated K+channels(BKCa)were examined in rat cerebral vascular smooth muscle cells(VSMCs).Results An increase of cytoplasmic Ca^(2+) and a decrease of mitochondrial/sarcoplasmic reticulum(SR)Ca^(2+) were observed in HU rat cerebral VSMCs.The abundance of fusion proteins(mitofusin 1/2[MFN1/2])and fission proteins(dynamin-related protein 1[DRP1]and fission-mitochondrial 1[FIS1])was significantly downregulated and upregulated,respectively in HU rat cerebral VSMCs.The cerebrovascular contractile responses to vasoconstrictors were enhanced in HU rats compared to control rats,and IP3 R protein/mRNA levels were significantly upregulated.The current densities and open probabilities of KV and BKCa decreased and increased,respectively.Treatment with the mitochondrial-targeted antioxidant mitoTEMPO attenuated mitochondrial fission by upregulating MFN1/2 and downregulating DRP1/FIS1.It also decreased IP3 R expression levels and restored the activities of the KV and BKCa channels.MitoTEMPO restored the Ca^(2+) distribution in VSMCs and attenuated the enhanced vasoconstriction in HU rat cerebral arteries.Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.

Calcium intake,calcium homeostasis and health

Calcium,as the most abundant mineral in human body,is involved in many physiological and pathological processes.Here,we reviewed the key mechanisms of calcium homeostasis,including calcium sensing receptor regulation,intestinal calcium absorption,renal calcium reabsorption and bone calcium resorption.We further discussed the roles of dietary calcium and vitamin D in diseases associated with dysfunctional regulation of calcium.However,the over-dosed consumption of calcium could increase the risks for a series of diseases,such as kidney stone,myocardial infarction and stroke.

Latest assessment methods for mitochondrial homeostasis in cognitive diseases

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

Liraglutide directly protects cardiomyocytes against reperfusion injury possibly via modulation of intracellular calcium homeostasis

Background Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglntide can perform direct protective effects on cardiomyocytes against reperfusion injury. Methods In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation （H/R） induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential （AWm） and intracellular reactive oxygen species （ROS） was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2＋ concentration and calcium transient. Immtmofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2＋-ATPase （SERCA2a）. In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. Results In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. △mψ of cardiomyocytes was higher in liraglntide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2＋ overload and improved calcium transient compared with H/R group, lmmunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Conclusions Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.

Towards carbon neutrality of calcium carbide-based acetylene production with sustainable biomass resources

Acetylene is produced from the reaction between calcium carbide(CaC_(2))and water,while the production of CaC_(2) generates significant amount of carbon dioxide not only because it is an energy-intensive process but also the raw material for CaC_(2) synthesis is from coal.Here,a comprehensive biomass-to-acetylene process was constructed that integrated several units including biomass pyrolysis,oxygen-thermal CaC_(2) fabrication and calcium looping.For comparison,a coal-to-acetylene process was also established by using coal as feedstock.The carbon efficiency,energy efficiency and environmental impacts of the bio-based calcium carbide acetylene(BCCA)and coal-based calcium carbide acetylene(CCCA)processes were systematically analyzed.Moreover,the environmental impacts were further evaluated by applying thermal integration at system level and energy substitution in CaC_(2) furnace.Even though the BCCA process showed lower carbon efficiency and energy efficiency than that of the CCCA process,life cycle assessment demonstrated the BCCA(1.873 kgCO_(2eq) kg-prod^(-1))a lower carbon footprint process which is 0.366 kgCO_(2eq) kg-prod^(-1) lower compared to the CCCA process.With sustainable energy(biomass power)substitution in CaC_(2) furnace,an even lower GWP value of 1.377 kgCO_(2eq) kg-prod^(-1) can be achieved in BCCA process.This work performed a systematic analysis on integrating biomass into industrial acetylene production,and revealed the positive role of biomass as raw material(carbon)and energy supplier.

Mutant amyloid precursor protein and presenilin-1 genes effect on ischemia vulnerability via calcium homeostasis disturbance

BACKGROUND： Previous studies have demonstrated that mutant amyloid precursor protein （APP） or presenilin-1 （PS1） genes increase susceptibility to ischemic brain damage induced by middle cerebral artery occlusion. Possible mechanisms include over-production of beta-amyloid peptide （Aβ）. OBJECTIVE： Because Aβ is over-produced in the APP/PS1 double-transgenic mouse, the present study focused on mechanisms of increased ischemic damage due to mutant APP and PS1 genes by measuring oxidative stress, mitochondrial function, and calcium homeostasis. DESIGN, TIME AND SETTING： The non-randomized, controlled, in vivo and in vitro experiments were performed at the Medical Research Center, Second Clinical College, Jinan University between May and October 2008. MATERIALS： Male APP transgenic mice carrying the mutant 695swe gene and female PS1 transgenic mice carrying the mutant Leu235Pro gene were donated from the University of Hong Kong. SHSY5Y human neureblastoma cells were purchased from ATCC （Manassas, VA, USA）, and Aβ1-42 was obtained from Sigma-Aldrich （St. Louis, MO, USA）. METHODS： APP transgenic mice were mated with PS1 transgenic mice to produce APP/PS1 double-transgenic mice and wildtype littermates mice. The photothrombotic stroke model was induced in six APP/PS1 double-transgenic and 6 wildtype littermates mice. SHSY5Y human neuroblastoma cells were cultured in vitro, and were divided into 4 groups： Aβ group, cells were exposed to 5 pmol/L Aβ for 24 hours; oxygen-glucose deprivation （OGD） group, cells were exposed to OGD for 1 hour after treatment with sterile, ultra-pure water for 24 hours; OGD＋Aβ group, cells were exposed to OGD and Aβfor 1 hour after treatment with 5 pmol/L Aβ for 24 hours; sham control group： cells were exposed to sterile, ultra-pure water for 25 hours. OGD was achieved by exposing the cells to glucose-free DMEM and placing the cells in an anaerobic chamber flushed with 5% CO2 and 95% N2 （v/v） at 37 ℃ for 1 hour. MAIN OUTCOME MEASURES： TTC staining was used to measure infarct volume 7 days after photothrombotic stroke. Cell viability was evaluated using the MTT kit. Opening of the mitochondrial permeability transition pore, intracellular concentration of superoxide anion, and calcium after OGD were detected with fluorescence intensity of calcein-AM, hydroethidine, and fluo-3/AM. RESULTS： At 7 days after stroke, total infarct volume and cortical infarct volume were significantly greater in the APP/PS1 transgenic mice compared with the wildtype littermates mice （P 〈 0.01）. Aβ, OGD, and Aβ ＋ OGD significantly decreased cell viability and increased fluorescence intensity of hydroethidine and fluo-3/AM （P 〈 0.01）. Compared with the Aβ or OGD group, Aβ ＋ OGD significantly decreased cell viability （P 〈 0.01） and significantly increased fluorescence intensity of calcein-AM, hydroethidine, and fluo-3/AM （P 〈 0.01 or P 〈 0.05）. CONCLUSION： The APP/PS1 double-transgenic mice were more vulnerable to ischemia. The possible mechanisms included enhanced opening of the mitochondrial permeability transition pore, overproduction of superoxide anion due to pore opening, and disturbed calcium homeostasis induced by excess superoxide anion.

Effects of inhibition of glycolysis on calcium homeostasis and functional recovery of stunned myocardium

Objective:To observe the effects of inhibition of glycolysis with iodoacetate (IAA) on calcium homeostasis and functional recovery of stunned myocardium in anesthetized dogs. Methods: Atomic absorption spectrophotometry was employed to measure myocyte calcium and magnesium contents. Hemodynamics were monitored with a multichannel electrophysiologic recorder. Results: In nonischemic canine hearts (control), IAA's inhibition of glycolysis failed to change the [Ca2+] and [Mg2+] levels and cardiac functional conditions, whereas in hearts subjected to 15-minute ischemia , [Ca2+] increased from nonischemic 1.40±0. 20μmol/g to ischemic 1.80±0.17 μmol/g (P<0. 05), while [Mg2+] decreased. After 30 min of reperfusion,[Ca2+] continued to increase from 1.57±0.21 μmol/g (nonischemic area)to 2. 26±0. 09 μmol/g (abnormal area) and 60 min of reperfusion saw a slight restoration (1.54±0. 16 μmol/g in nonischemic area and 2. 21±0.20 μmol/g in abnormal area). In the glycolysis-inhibiting group, the calcium level registered a significant rise after 30 min of reperfusion: 1.57±0.07 μmol/g in nonischemic area and 2. 90? 0.25 μmol/g in abnormal area (P<0. 01).There was a significant difference between the glycolysis-inhibiting group and the group to which IAA was not applied. [Mg2+] maintained at a relatively low level and registered a more remarkable drop during inhibition of glycolysis, P<0.01 in comparison with the non IAA-administered group,suggesting that inhibition of glycolysis could cause severe calcium overload to sustain, in addition to an obvious harm to cardiac function. Left ventricular end-diastolic pressure and diastolic factor T were augmented andp/dt(max)declined. Conclusion: Since in vivo inhibition of glycolysis seemed to lead to severe calcium overload and hemodynamics changes,it might indicate that glycolysis played an importent role in the restoration of calcium homeostasis in postischemic myocardium,and that ATP derived from glycolysis took a significant part in myocardial ion transport both at the stage of ischemia and the early stage of reperfusion and in cardiac functional recovery.

Calcium Homeostasis in Articular Chondrocytes of Two Different Animal Species

Introduction: Intracellular calcium concentration ([Ca2+]i) is a critical parameter in cellular homeostasis, including articular chondrocytes. Perturbed [Ca2+]i of chondrocytes may be associated with joint disease. The objective of the study was to compare large animal models for investigating Ca2+ homeostasis in chondrocytes. Materials and Methods: The gross anatomy of the metacarpophalangeal joint (MCP) of cattle and sheep was compared, along with the effect of various manoeuvres used to study the mechanisms of Ca2+ homeostasis in chondrocytes from load-bearing areas. The gross anatomy was observed before and after dissection, and internal architecture was examined after sectioning. Cartilage thickness was measured with a digital micrometer. Chondrocyte yield was determined after isolation. Chondrocytes were incubated with Fura-2 and Ca2+i followed in different extracellular conditions. A hypotonic shock (HTS) was used to mimic removal of a load. Results: The results showed that ovids and bovids were skeletally immature and aspects of Ca2+ homeostasis were similar. Ovine chondrocytes had higher resting fluorescence, consistent with elevated resting Ca2+ levels. Results from ion substitution experiments were consistent with a role for Na+/Ca2+ exchange, and swelling-induced Ca2+ enters into the cytoplasm via the plasma membrane and intracellular stores. Conclusions: Ca2+ homeostasis in chondrocytes from both species behaved in a similar manner to HTS and ion substitutions. Differences in resting [Ca2+]i could be associated with species, stage of maturation, or Fura-2 itself and require further investigation. These findings contribute to our understanding of the physiology of articular cartilage in different species, and their potential use as models for studying joint disease in humans.

Regulatory mechanisms of iron homeostasis in maize mediated by ZmFIT

Regulation of iron homeostasis in maize remains unclear,despite the known roles of FER-Like Fe deficiency-induced transcription factor(FIT)in Arabidopsis and rice.ZmFIT,like At FIT and Os FIT,interacts with iron-related transcription factors 2(ZmIRO2).Here,we investigate the involvement of ZmFIT in iron homeostasis.Mutant ZmFIT lines exhibiting symptoms of Fe deficiency had reduced shoot iron content.Transcriptome analysis revealed downregulation of Fe deficiency-responsive genes in the roots of a Zmfit mutant.ZmFIT facilitates the nuclear translocation of ZmIRO2 to activate transcription of downstream genes under Fe-deficient conditions.Our findings suggest that ZmFIT,by interaction with ZmIRO2,mediates iron homeostasis in maize.Notably,the binding and activation mechanisms of ZmFIT resemble those in Arabidopsis but differ from those in rice,whereas downstream genes regulated by ZmFIT show similarities to rice but differences from Arabidopsis.In brief,ZmFIT,orthgologs of Os FIT and At FIT in rice and maize,respectively,regulates iron uptake and homeostasis in maize,but with variations.

Elaidic acid leads to mitochondrial dysfunction via mitochondria-associated membranes triggers disruption of mitochondrial calcium fluxes

Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.

Characteristics of a Critical Calcium Transportation Regulator: Plasma Membrane Ca²⁺-ATPase Involved in Calcium Homeostasis from <i>Hyriopsis cumingii</i>(Lea)

Plasma Membrane Calcium ATPase (PMCA) plays a critical role in transporting Ca2+ out of the cytosol across the plasma membrane. Here, a full-length cDNA sequence of plasma membrane Ca2+-ATPase gene was isolated from the gill of Hyriopsis cumingii (HcPMCA) by using SMART RACE technique. The entire cDNA was 5230 bp, including a 417-bp 5'-UTR, a 3588-bp ORF and a 1225-bp 3'-UTR, encoding a 1195-amino acid protein, and no putative signal peptide was predicted. Compared with PMCA homologs from seawater mollusks, HcPMCA had high similarity with them in both sequence and structure. Tissue-specific expression analysis revealed that HcPMCA mRNA was detected in all the sampled tissues, but was prominently expressed in the gill and mantle. When exposed to a serie of increasing Ca2+ that lasted for 7 days, the mRNA expression of HcPMCA in the mantle was slightly downregulated, but peaked at 60 mg/L. Moreover, the temporal expression of HcPMCA transcripts in the mantle after 60 mg/L Ca2+ exposure was shown to be bell-shaped, which was slightly downregulated at 24 h, but upregulated from 24 h to 48 h post-treatment, peaking at 48 h. The result of present study provides useful information for further studies on function and regulation mechanism of HcPMCA gene.

Calmodulins and calmodulin-like proteins-mediated plant organellar calcium signaling networks under abiotic stress

Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting Ca~(2+)signals,regulatory roles of Ca Ms and CMLs,binding targets,and Ca~(2+)networks under abiotic stress in organelles.