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Cardiomyocytes and mitochondria

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https://read.qxmd.com/read/30771306/spred2-deficiency-elicits-cardiac-arrhythmias-and-premature-death-via-impaired-autophagy
#1
Melanie Ullrich, Benjamin Aßmus, Anne Marie Augustin, Hannes Häbich, Marco Abeßer, Jorge Martin Machado, Franziska Werner, Ralf Erkens, Anahi-Paula Arias-Loza, Sandra Umbenhauer, Helga Wagner, Peter M Benz, Andreas Unger, Wolfgang A Linke, Stefan Frantz, Hideo A Baba, Michaela Kuhn, Kai Schuh
Cardiac functionality is dependent on a balanced protein turnover. Accordingly, regulated protein decay is critical to maintain cardiac function. Here we demonstrate that deficiency of SPRED2, an intracellular repressor of ERK-MAPK signaling markedly expressed in human heart, resulted in impaired autophagy, heart failure, and shortened lifespan. SPRED2-/- mice showed cardiomyocyte hypertrophy, cardiac fibrosis, impaired electrical excitability, and severe arrhythmias. Mechanistically, cardiomyocyte dysfunction resulted from ERK hyperactivation and dysregulated autophagy, observed as accumulation of vesicles, vacuolar structures, and degenerated mitochondria...
February 13, 2019: Journal of Molecular and Cellular Cardiology
https://read.qxmd.com/read/30770570/camkii-does-not-control-mitochondrial-ca-2-uptake-in-cardiac-myocytes
#2
Alexander G Nickel, Michael Kohlhaas, Edoardo Bertero, Daniel Wilhelm, Michael Wagner, Vasco Sequeira, Michael M Kreusser, Matthias Dewenter, Reinhard Kappl, Markus Hoth, Jan Dudek, Johannes Backs, Christoph Maack
KEY POINTS: Mitochondrial Ca2+ uptake stimulates the Krebs cycle to regenerate the reduced forms of pyridine nucleotides (NADH, NADPH and FADH2 ) required for ATP production and ROS elimination. It was previously proposed that Ca2+ /calmodulin-dependent protein kinase II (CaMKII) regulates mitochondrial Ca2+ uptake via MCU phosphorylation. We used two mouse models with either global deletion of CaMKIIδ (CaMKIIδ KO) or cardiomyocyte-specific deletion of CaMKIIδ and γ (CaMKIIδ/γ DKO) to interrogate whether CaMKII controls mitochondrial Ca2+ uptake in isolated mitochondria and during β-adrenergic stimulation in cardiac myocytes...
February 16, 2019: Journal of Physiology
https://read.qxmd.com/read/30767143/the-different-response-of-cardiomyocytes-and-cardiac-fibroblasts-to-mitochondria-inhibition-and-the-underlying-role-of-stat3
#3
Jing Zhao, Jin-Lai Gao, Jun-Xue Zhu, Hai-Bin Zhu, Xuan Peng, Man Jiang, Yao Fu, Juan Xu, Xi-Hai Mao, Nan Hu, Ming-Hui Ma, De-Li Dong
Cardiomyocyte loss and cardiac fibrosis are the main characteristics of cardiac ischemia and heart failure, and mitochondrial function of cardiomyocytes is impaired in cardiac ischemia and heart failure, so the aim of this study is to identify fate variability of cardiomyocytes and cardiac fibroblasts with mitochondria inhibition and explore the underlying mechanism. The mitochondrial respiratory function was measured by using Oxygraph-2k high-resolution respirometry. The STAT3 expression and activity were evaluated by western blot...
February 14, 2019: Basic Research in Cardiology
https://read.qxmd.com/read/30765730/doxorubicin-induced-cardiomyopathy-associated-with-inhibition-of-autophagic-degradation-process-and-defects-in-mitochondrial-respiration
#4
Chowdhury S Abdullah, Shafiul Alam, Richa Aishwarya, Sumitra Miriyala, Mohammad Alfrad Nobel Bhuiyan, Manikandan Panchatcharam, Christopher B Pattillo, A Wayne Orr, Junichi Sadoshima, Joseph A Hill, Md Shenuarin Bhuiyan
Doxorubicin (Dox) is a highly effective anticancer drug but cause acute ventricular dysfunction, and also induce late-onset cardiomyopathy and heart failure. Despite extensive studies, the pathogenic sequelae leading to the progression of Dox-associated cardiomyopathy remains unknown. We assessed temporal changes in autophagy, mitochondrial dynamics, and bioenergetics in mouse models of acute and chronic Dox-cardiomyopathy. Time course study of acute Dox-treatment showed accumulation of LC3B II in heart lysates...
February 14, 2019: Scientific Reports
https://read.qxmd.com/read/30745856/sirt6-suppresses-high-glucose-induced-mitochondrial-dysfunction-and-apoptosis-in-podocytes-through-ampk-activation
#5
Yanqin Fan, Qian Yang, Yingjie Yang, Zhao Gao, Yiqiong Ma, Lu Zhang, Wei Liang, Guohua Ding
Previous studies have shown that mitochondrial dysfunction plays an important role in high- glucose(HG)-induced podocyte injury and thus contributes to the progression of diabetic nephropathy(DN). The histone deacetylase Sirtuin6 (Sirt6) has been revealed to have an essential role in the regulation of mitochondrial function in skeletal muscle and cardiomyocytes. However, its specific role in mitochondrial homeostasis in podocytes is undetermined. Here, we aimeds to explore the physiological function of Sirt6 in podocyte mitochondria and apoptosis under HG conditions and explore the possible mechanism...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30745854/reactive-oxygen-species-related-noncoding-rnas-as-regulators-of-cardiovascular-diseases
#6
REVIEW
Yanhan Dong, Wenhua Xu, Cuiyun Liu, Peijun Liu, Peifeng Li, Kun Wang
Reactive oxygen species (ROS) are a class of reactive molecules that have been implicated in a variety of cardiovascular diseases, accompanied by disorder of multiple signaling events. As cardiomyocytes maintain abundant of mitochondria, which supply the major source of endogenous ROS, oxidative damage to mitochondria often drives apoptotic cell death and initiates cardiac pathology. In recent years, non-coding RNAs (ncRNAs) have received much attention to uncover their roles in regulating gene expression during those pathological events in the heart, such as myocardial infarction, cardiac hypertrophy, and heart failure...
2019: International Journal of Biological Sciences
https://read.qxmd.com/read/30713257/resistance-of-fetal-guinea-pig-ventricular-myocardium-to-hypoxia-maintained-intracellular-atp-prevents-the-opening-of-atp-sensitive-potassium-channels
#7
Naoki Agata, Yoshimitsu Kato, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
The presence and function of the ATP-sensitive potassium channel current (IKATP ) were examined in the guinea pig myocardium to clarify the mechanisms for the resistance of the fetal myocardium to hypoxia. Experimental hypoxia markedly reduced the action potential duration and contractile force in isolated ventricular myocardium from the adult, but only moderately in those from the fetus. In isolated ventricular cardiomyocytes, the density of the IKATP activated by cromakalim, as well as their sensitivity to intracellular ATP concentration, were not different between the fetus and adult...
2019: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/30699925/delayed-onset-of-age-dependent-changes-in-ultrastructure-of-myocardial-mitochondria-as-one-of-the-neotenic-features-in-naked-mole-rats-heterocephalus-glaber
#8
Lora Bakeeva, Valeria Vays, Irina Vangeli, Chupalav Eldarov, Susanne Holtze, Thomas Hildebrandt, Vladimir Skulachev
In this study, the ultrastructure of mitochondria in cardiomyocytes of naked mole rats ( Heterocephalus glaber ) aged from 6 months to 11 years was examined. Mitochondria in cardiomyocytes of naked mole rats have a specific ultrastructure that is different from those in cardiomyocytes of other mammalian species studied to date. In contrast to mitochondria of other mammalian cardiomyocytes, where the internal space is completely filled by tightly packed parallel rows of cristae, mitochondria in cardiomyocytes of naked mole rats have a chaotic pattern of cristae organization with wave-like contours...
January 29, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30692261/ferroptosis-as-a-target-for-protection-against-cardiomyopathy
#9
Xuexian Fang, Hao Wang, Dan Han, Enjun Xie, Xiang Yang, Jiayu Wei, Shanshan Gu, Feng Gao, Nali Zhu, Xiangju Yin, Qi Cheng, Pan Zhang, Wei Dai, Jinghai Chen, Fuquan Yang, Huang-Tian Yang, Andreas Linkermann, Wei Gu, Junxia Min, Fudi Wang
Heart disease is the leading cause of death worldwide. A key pathogenic factor in the development of lethal heart failure is loss of terminally differentiated cardiomyocytes. However, mechanisms of cardiomyocyte death remain unclear. Here, we discovered and demonstrated that ferroptosis, a programmed iron-dependent cell death, as a mechanism in murine models of doxorubicin (DOX)- and ischemia/reperfusion (I/R)-induced cardiomyopathy. In canonical apoptosis and/or necroptosis-defective Ripk3 -/- , Mlkl -/- , or Fadd -/- Mlkl -/- mice, DOX-treated cardiomyocytes showed features of typical ferroptotic cell death...
January 28, 2019: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30688415/effects-of-elamipretide-on-skeletal-muscle-in-dogs-with-experimentally-induced-heart-failure
#10
Hani N Sabbah, Ramesh C Gupta, Vinita Singh-Gupta, Kefei Zhang
AIMS: Elamipretide (ELAM), an aromatic-cationic tetrapeptide, interacts with cardiolipin and normalizes dysfunctional mitochondria of cardiomyocytes. This study examined the effects of ELAM on skeletal muscle mitochondria function in dogs with chronic heart failure (HF). METHODS AND RESULTS: Studies were performed in skeletal muscle biopsy specimens obtained from normal dogs (n = 7) and dogs with chronic intracoronary microembolization-induced HF (n = 14) treated with subcutaneous ELAM 0...
January 28, 2019: ESC Heart Failure
https://read.qxmd.com/read/30685253/sr-mitochondria-communication-in-adult-cardiomyocytes-a-close-relationship-where-the-ca-2-has-a-lot-to-say
#11
REVIEW
Sergio De la Fuente, Shey-Shing Sheu
In adult cardiomyocytes, T-tubules, junctional sarcoplasmic reticulum (jSR), and mitochondria juxtapose each other and form a unique and highly repetitive functional structure along the cell. The close apposition between jSR and mitochondria creates high Ca2+ microdomains at the contact sites, increasing the efficiency of the excitation-contraction-bioenergetics coupling, where the Ca2+ transfer from SR to mitochondria plays a critical role. The SR-mitochondria contacts are established through protein tethers, with mitofusin 2 the most studied SR-mitochondrial "bridge", albeit controversial...
January 24, 2019: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/30684463/role-of-mitochondrial-ca-2-homeostasis-in-cardiac-muscles
#12
REVIEW
Jessica L Cao, Stephanie M Adaniya, Michael W Cypress, Yuta Suzuki, Yoichiro Kusakari, Bong Sook Jhun, Jin O-Uchi
Recent discoveries of the molecular identity of mitochondrial Ca2+ influx/efflux mechanisms have placed mitochondrial Ca2+ transport at center stage in views of cellular regulation in various cell-types/tissues. Indeed, mitochondria in cardiac muscles also possess the molecular components for efficient uptake and extraction of Ca2+ . Over the last several years, multiple groups have taken advantage of newly available molecular information about these proteins and applied genetic tools to delineate the precise mechanisms for mitochondrial Ca2+ handling in cardiomyocytes and its contribution to excitation-contraction/metabolism coupling in the heart...
January 23, 2019: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/30683110/mitochondria-targeted-cyclosporin-a-delivery-system-to-treat-myocardial-ischemia-reperfusion-injury-of-rats
#13
Chang-Xiong Zhang, Ying Cheng, Dao-Zhou Liu, Miao Liu, Han Cui, Bang-le Zhang, Qi-Bing Mei, Si-Yuan Zhou
BACKGROUND: Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI...
January 25, 2019: Journal of Nanobiotechnology
https://read.qxmd.com/read/30664839/mitochondrial-dynamics-and-inter-mitochondrial-communication-in-the-heart
#14
REVIEW
Yang-Po Cao, Ming Zheng
Mitochondria are organelles highly dynamic in most types of cells, constantly changing morphology and forming dynamically continuous networks. Defects of mitochondrial dynamics are associated with various human diseases including neurodegenerative diseases and cardiovascular diseases. In the heart, mitochondria are rigidly organized between myofilaments into a crystal-like lattice pattern, the apparently limited mitochondrial movement raises the question of whether mitochondria communicate with each other dynamically...
January 18, 2019: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/30661785/sphingosine-1-phosphate-attenuates-hypoxia-reoxygenation-induced-cardiomyocyte-injury-via-a-mitochondrial-pathway
#15
Mengran Ke, Qiqi Tang, Ziang Pan, Yongqiang Yin, Lizhi Zhang, Ke Wen
Our previous study showed that Sphingosine-1-phosphate (S1P) could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury via the JAK-STAT pathway and maintain normal myocardial mitochondria integrity in vivo. However, it is not known yet whether S1P can relieve mitochondrial dysfunction via the mitochondrial apoptotic pathway and its detailed mechanism remains to be investigated. The aim of this study was to demonstrate the mitochondrial protective effects of S1P in a cardiomyocyte H/R injury model...
January 17, 2019: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/30651835/eriodictyol-protects-h9c2-cardiomyocytes-against-the-injury-induced-by-hypoxia-reoxygenation-by-improving-the-dysfunction-of-mitochondria
#16
Yanli Xie, Rongwei Ji, Minghui Han
Myocardial infarction is a leading cause of mortality worldwide, while myocardial ischemia and timely reperfusion contribute to myocardial injury. The mitochondria are involved in the injury and mediate the apoptosis of cardiomyocytes. In order to develop novel therapeutic approaches for myocardial infarction, the present study evaluated the myocardial protective effects of eriodictyol and investigated relevant mechanisms in H9c2 cardiomyocytes. As a result, eriodictyol was observed to improve the H9c2 cardiomyocyte viability and block the leakage of cytosolic lactate dehydrogenase under hypoxia/reoxygenation...
January 2019: Experimental and Therapeutic Medicine
https://read.qxmd.com/read/30646747/hyperglycemia-driven-inhibition-of-amp-activated-protein-kinase-%C3%AE-2-induces-diabetic-cardiomyopathy-by-promoting-mitochondria-associated-endoplasmic-reticulum-membranes-in-vivo
#17
Shengnan Wu, Qiulun Lu, Ye Ding, Yin Wu, Yu Qiu, Pei Wang, Xiaoxiang Mao, Kai Huang, Zhonglin Xie, Ming-Hui Zou
BACKGROUND: FUN14 domain containing 1 (Fundc1), an outer mitochondrial membrane protein, is important for mitophagy and mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs). The roles of Fundc1 and MAMs in diabetic hearts remain unknown. The aims of this study therefore, were to determine if the diabetes-induced Fundc1 expression could increase MAM formation, and whether disruption of MAM formation improves diabetic cardiac function. METHODS: Levels of FUNDC1 were examined in the hearts from diabetic patients and nondiabetic donors...
January 16, 2019: Circulation
https://read.qxmd.com/read/30639669/mitochondria-targeted-antioxidant-delivery-for-precise-treatment-of-myocardial-ischemia-reperfusion-injurythrough-a-multistage-continuous-targeted-strategy
#18
Ying Cheng, Dao-Zhou Liu, Chang-Xiong Zhang, Han Cui, Miao Liu, Bang-le Zhang, Qi-Bing Mei, Zi-Fan Lu, Si-Yuan Zhou
Efficient delivery of antioxidant drugs into mitochondria of ischemic cardiomyocytes where reactive oxygen species largely induced is a major challenge for precise treatment of myocardial ischemia-reperfusion injury. Herein, we report a smart dual-shell polymeric nanoparticle, MCTD-NPs, which utilizes multistage continuous targeted strategy to deliver reactive oxygen species scavenger specifically to mitochondria of ischemic cardiomyocytes upon systemic administration. In vitro experiments indicated that the intracellular uptake of MCTD-NPs was specifically enhanced in hypoxia reoxygenation injured H9c2 cells...
January 9, 2019: Nanomedicine: Nanotechnology, Biology, and Medicine
https://read.qxmd.com/read/30639303/trimetazidine-and-l%C3%A2-carnitine-prevent-heart-aging-and-cardiac-metabolic-impairment-in-rats-via-regulating-cardiac-metabolic-substrates
#19
Xia Zhang, Chun Liu, Congcong Liu, Yan Wang, Wenhua Zhang, Yanqiu Xing
BACKGROUND: This study aimed to investigate the effects of trimetazidine and l‑carnitine on heart aging and cardiac metabolism in the natural aging rats and explore the possible mechanism regarding the regulation of cardiac metabolic substrates. METHODS: A total of 28 young (2-month-old) and 28 aged (14-month-old) male Sprague-Dawley rats were randomly allocated to the following groups: young control (YC, n = 8), young trimetazidine (YT, n = 10), young l‑carnitine (YL, n = 10), aging control (AC, n = 8), aging trimetazidine (AT, n = 10), and aging l‑carnitine (AL, n = 10)...
January 8, 2019: Experimental Gerontology
https://read.qxmd.com/read/30636491/quercetin-protects-cardiomyocytes-against-doxorubicin-induced-toxicity-by-suppressing-oxidative-stress-and-improving-mitochondrial-function-via-14-3-3%C3%AE
#20
Xuanying Chen, Xiaoping Peng, Yong Luo, Jiegen You, Dong Yin, Qiang Xu, Huan He, Ming He
Cardiotoxicity limits the clinical applications of doxorubicin (Dox), which mechanism might be excess generation of intracellular ROS. Quercetin (Que) is a flavonoid that possesses anti-oxidative activities, exerts myocardial protection. We hypothesized that the cardioprotection against Dox injury of Que involved 14-3-3γ, and mitochondria. To investigate the hypothesis, we treated primary cardiomyocytes with Dox and determined the effects of Que pretreatment with or without 14-3-3γ knockdown. We analyzed various cellular and molecular indexes...
January 14, 2019: Toxicology Mechanisms and Methods
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