Recent research advance in mitochondria Cx43 and its cardiovascular effects

Connexins are transmembrane proteins. The best-known function of connexins is to form gap junction channels. Cardiomyocytes predominantly express connexin 43 (Cx43). Recent studies show that Cx43 is not only present at the sarcolemma but is also detected in mitochondria of cardiomyocytes, at least in part in the inner mitochondrial membrane. Mitochondrial Cx43 plays a central role for triggering/mediating the cardioprotection by ischemic preconditioning (IPC), however the molecular mechanisms have not been elucidated in detail. The present article reviews the available evidence on the localization, the mechanism of transport, the phosphorylation status, the affecting factors and the physiological role of mitochondrial Cx43. These findings open a new field for investigating the previously unsuspected roles of Cx43 in mitochondria about their functions, regulation and molecular mechanisms involved in pathophysiology not only in myocardial ischaemia-reperfusion injury but also in other conditions in the cardiovascular system and beyond.     

The coordinated regulation between nuclear DNA and mitochondria DNA

The overall cellular gene expression is well realized by the coordinated regulation between nuclear DNA and mitochondria DNA. Coordinated regulation between two genomes plays a key role not only in mitochondria biogenesis and protein synthesis but also more importantly in the regulation of gene expression of mitochondria respiratory chain subunits in order to mediate the mitochondrial respiratory function. In the present review, we focus on the mechanism of coordinated regulation between two genomes.     

Progress in mitoepigenetic regulation and Alzheimer disease

Mitochondrion is an organelle containing its own genome in eukaryotic cells, which encodes 37 genes involved in mitochondrial functions. Mitoepigenetic regulation is a major form of mitochondrial genome-encoded genes that regulates the expression levels without altering the sequences of the genes. The mitoepigenetic regulation is involved in the occurrence and development of various diseases. This paper reviews the progress of mitoepigenetic regulation and Alzheimer disease.     

Roles of mitochondrial dysfunction in cardiovascular diseases

Mitochondria are important organelles of energy generation in eukaryocytes and play a pivotal role in cell calcium homeostasis, signal transduction and apoptotic regulation. The possible causes leading to mitochondrial dysfunction include oxidative stress, Ca2+ disorder, reduction of mitochondrial biosynthesis and mitochondrial DNA mutations, all of which are also closely related to the development of cardiovascular diseases. Understanding the mitochondrial dysfunction and its important role in cardiovascular diseases are very significant for elucidating the mechanisms of cardiovascular diseases.     

Effect of adipokine chemerin on mitochondrial dysfunction in cardiac H9C2 cells with hypertrophy

AIM To study the regulation of adipokine chemerin on mitochondrial function of rat cardiac H9C2 cells with hypertrophy, and to explore its effect on mitochondrial dysfunction in the H9C2 cells. METHODS In vitro cell experiments were performed, and the H9C2 cells were divided into normal group, chemerin group, angiotensin Ⅱ (Ang Ⅱ) model group and Ang Ⅱ+chemerin group. Immunohistochemistry and qPCR were used to identify whether the model was successfully constructed. The morphological changes of mitochondria in the H9C2 cells were observed under electron microscope. The mitochondrial membrane potential and membrane permeability were analyzed by flow cytometry. The activity of cytochrome C oxidase (COX) and succinate dehydrogenase (SDH) was measured by enzyme activity kit. RESULTS Compared with normal group, the mitochondrial structure in Ang Ⅱ group and chemerin group was seriously damaged, the permeability of mitochondrial membrane was significantly increased (P<0.01), and the mitochondrial membrane potential and the activity of COX and SDH were significantly reduced (P<0.01). Meanwhile, the mitochondrial damage in the H9C2 cells was more serious in Ang Ⅱ+chemirin group (P<0.05). CONCLUSION Chemerin stimulation not only induces cardiomyocyte hypertrophy, but also promote the pathological process of mitochondrial dysfunction in the myocardial cells with hypertrophy.     

Signaling pathways involved in mediating mitochondrial damage in diabetic kidney disease

Diabetic kidney disease （DKD） is one of the most common and serious chronic complications of diabetes and has gradually become the main cause of end-stage renal disease （ESRD）. As the center of energy and metabolism in cells, mitochondria have become the focus of the research on the pathogenesis of DKD in recent years. Current studies find that damage to mitochondria, such as DNA mutations, structural damage, oxidative stress imbalance, etc, leads to apoptosis of kidney cells, thus causing the loss of kidney function. In the process of mitochondrial damage, a series of important signaling pathways are involved, and exploring these signaling pathways would help us better understand the pathogenesis of DKD and find new therapeutic targets. In this article, the important signaling pathways associated with mitochondrial damage are reviewed.     

Effects of nitric oxide on mitochondrial function in cardiomyocytes: pathophysiological relevance

It is now clear that both endogenous and exogenous sources of nitric oxide (NO) exert important modulatory effects on cardiac mitochondrial function. There is also growing evidence that NO can be produced within the mitochondria themselves. NO can influence respiratory activity, both through direct effects on the respiratory chain or indirectly via modulation of mitochondrial calcium accumulation. At pathological concentrations, NO causes irreversible alterations in respiratory function and also interacts with reactive oxygen species (ROS) to form reactive nitrogen species (RNS), which may further impair mitochondrial respiration and even lead to open the mitochondrial permeability transition pore and induce cell death. Diabetes, aging, myocardial ischemia, and heart failure are all associated with altered ROS generation, which can alter the delicate regulatory balance of effects of NO in the mitochondria.     

Research progress of mitochondrial biogenesis and cerebral ischemia/reperfusion injury

Mitochondria are important intracellular energy supply organelles. As semi-autonomous organelles, the mitochondrial biogenesis, damage and clearance were the dynamic processes, which are dual-regulated by mitochondrial genes and nuclear genes, and maintain mitochondrial homeostasis according to the needs of the cells for energy. Recent studies provide evidence that the disorder of mitochondrial biogenesis in the neurons participates in the pathological process after cerebral ischemia/reperfusion, resulting in metabolic disturbance and cell apoptosis. This paper reviews the research progress of mitochondrion and cerebral ischemia/reperfusion injury.     

Effects of diazoxide preconditioning on mitochondrial respiratory function and enzyme activity in rats

AIM: To investigate the effects of the selective mitochondrial ATP-sensitive K+ channels opener diazoxide on mitochondrial respiratory function and enzyme activity in isolated rat myocardium under ischemia/reperfusion.METHODS: Observation was made on rat hearts perfused with Langendorff apparatus.72 Sprague-Dawley (SD) rats were randomly divided into 4 groups: normal group (NOR),ischemia reperfusion (IR),diazoxide group (DIA) and 5-hydroxydecanoate (5-HD) antagonized diazoxide group (5HD-DIA).Hearts isolated from SD rats were mounted on a Langendorff apparatus and started with a 20 min perfusion for equilibration.NOR went on perfusion for another 100 min after equilibration.IR underwent 40 min global ischemia and followed by 30 min reperfusion after 30 min stabilization.DIA was administered with K-H solution containing diazoxide at concentration of 50 μmol/L for 10 min before ischemia and reperfusion.5HD-DIA was infused with 100 μmol/L 5-HD (a specific mitochondrial ATP sensitive K+ channel blocker) and the same procedure was carried out as DIA group.Hearts were taken down to extract mitochondrial at the end-equation,before ischemia and at the end-reperfusion for determination of mitochondrial respiratory function and the enzyme activity of mitochondria.RESULTS: At the end of reperfusion,mitochondrial respiratory function (mitochondrial respiratory control rate,P/O ratio and state 3 respiration) and mitochondrial enzyme activity (NADH oxidase,succinate oxidase and cytochrome C oxidase) in DIA group were better than those in IR group and 5HD-DIA group (P<0.05),but worse than those NOR group (P<0.01).No significant difference in all parameters was observed between IR and 5HD-DIA (P>0.05).CONCLUSION: Preconditioning with mitochondrial ATP sensitive potassium channel opener,diazoxide,protects rat heart mitochondria against ischemia-reperfusion injury.The mechanisms are involved in the safeguarding of respiratory function and activity of enzymes of respiratory chain.     

Protective effect of astragalus polysaccharide on mitochondria and lysosome in H2O2-stressed skin fibroblasts

AIM: To verify the protection of astragalus polysaccharide (APS) on H2O2-stressed skin fibroblasts. METHODS: A model of acute H2O2 stress in primary skin fibroblast was used at concentration of 0.5 mmol/L by 30 min incubation. Dose responses of APS on cell survival was measured by MTT, cell death was evaluated by DAPI, and effect of APS on mitochondria, mitochondrial membrane potential and lysosome stabilization were measured by confocal microscopy. RESULTS: APS improved cell survival in a dose-dependent manner, starting at 0.5 mg/L and with a maximum at 1 mg/L. Moreover, APS inhibited mitochondrial membrane potential collapse, protected mitochondrial morphology and stablized lysosomal membrane. CONCLUSION: The results suggest the existence, at the mitochondria-lysosome level, of a new pathway of apoptotic regulation by APS. This might constitute a new therapeutic target where oxidative stress and lysosomal impairment are involved.     

甜瓜属线粒体基因组的父系遗传特性

为分析甜瓜属线粒体基因组的遗传特性,选取甜瓜属11个不同种植物为试验材料,采用成熟花粉DAPI压片染色方法结合树脂半薄切片MTG-DAPI双染色技术,观察花粉贴壁期和成熟期细胞中的线粒体分布。结果显示,所涉及的11种甜瓜属植物均同黄瓜一样,成熟花粉细胞生殖核周围或精细胞中存在线粒体DNA;而作为对照的南瓜和西葫芦的花粉细胞发育到成熟期时生殖核周围没有任何细胞器DNA。上述结果表明,甜瓜属植物线粒体DNA有可能通过花粉进行遗传和散布。这个结果将线粒体基因组父系遗传潜力特性扩展到甜瓜属,为进一步探究植物线粒体基因组的父系遗传机制奠定基础。     

MADS-box转录因子在果实成熟及品质形成中的调控作用研究进展

近年来关于MADS-box转录因子的研究已陆续从花器官的形成扩展至植物生长发育的全过程,其中参与果实成熟与品质调控是研究的热点之一。综述了MADS-box转录因子参与调控果实品质形成的研究进展,讨论了该基因家族在果实品质调控研究方面存在的主要问题,明确了其未来研究的主要方向。     

Advances in function of circular RNA and regulation of atherosclerosis development

Atherosclerosis is one of the cardiovascular diseases that seriously endanger human health. The pathogenesis of atherosclerosis is very complicated and related to a variety of risk factors. In recent years, many studies have found that circular RNAs play an important regulatory role in the occurrence and development of atherosclerosis by inducing proliferation, differentiation, migration and apoptosis of vascular smooth muscle cells, endothelial cells and macrophages. This article reviews the basic functions of circular RNAs and its recent research on the regulation of atherosclerosis.     

Role of mitochondrial dysfunction in genesis of severe shock

The high mortality is a leading element of human health that follows severe shock even after blood transfusion and other anti-shock therapy. Therefore, to find out the mechanism of high mortality in severe shock is very critical. As a hotspot in recent years, mitochondrial function has important value in the genesis of many diseases, such as cardiovascular diseases, diabetes mellitus, Alzheimer disease, Parkinson disease, nonalcoholic steatohepatitis and so on. Mitochondrial dysfunction often takes place in relation to the opening of mitochondrial permeability transition pore with intracellular low ATP content in severe shock. The consequence of intracellular low ATP content may lead to the dysfunction of various organs with difficult treatment of severe shock. Therefore, protection against mitochondrial damage is a novel approach for treatment of severe shock. This article summarizes the concept, pathogenesis, detection variables and treatment of mitochondrial dysfunction in severe shock.     

Insulin-like growth factor I protects neonatal rat cardiomyocytes from apoptosis through improvement of mitochondrial function

AIM：To investigate whether mitochondrial mechanism is involved in the anti-apoptotic effect of insulin-like growth factor I (IGF-I) on cardiomyocytes. METHODS：Primary neonatal rat cardiomyocytes (NRCMs) were cultured and treated with 200 μmol/L hydrogen peroxide (H2O2) to induce apoptosis. Kruppel-like factor 9 (KLF9)-specific siRNA was transfected into the cells by Lipofectamine 2000. The mitochondrial function was measured by JC-1 mitochondrial membrane potential (MMP) assay. The mitochondrial morphology was observed by transmission electron microscopy. Myocardial cell apoptosis was detected by Annexin V-FITC/PI dual staining, caspase-3 activity assay, DNA-ladder analysis and Hoechst 33258 staining. RESULTS：The apoptosis of NRCMs was induced by H2O2, with MMP decreased by (24.0±1.6)% compared with control group. The fall rates of MMP in IGF-I group and KLF9 siRNA group were (18.3±1.2)% and (15.2±1.2)%, respectively (both P<0.01 vs H2O2 group), and improved mitochondrial morphology, decreased caspase-3 activity, attenuated DNA fragmentation and reduced apoptotic bodies were also observed in these two groups. The apoptotic rates of NRCMs in IGF-I group and KLF9 siRNA group were (22.4±4.2)% and (32.5±3.5)%, respectively, both lower than that in H2O2 group ［(42.5±1.8)%, P<0.01］. The anti-apoptotic effect of KLF9 silencing on NRCMs was consistent with that of IGF-I treatment. CONCLUSION：IGF-I protects NRCMs from apoptosis through down-regulating KLF9 expression and improving mitochondrial function.     

Fibroblasts function as "sentinel cell" in inflammatory reaction

The fibroblasts have long been considered as structural elements and playing a main role in wound healing. Recent studies indicated that fibroblasts are heterogenic cells and function as resident sentinel cells in inflammatory reaction. When activated by substances released during tissue injury or derived from infectious microorganisms or by proinflammatory cytokines, tissuespecific fibroblasts can transiently produce certain chemokines and initiate a cascade of inflammatory reaction. In addition fibroblasts can produce prostanoids that participate in inflammatory and immune responses. In this review, the new role of fibroblasts in regulation of inflammation and immune reactions and possible molecular mechanism will be discuss.