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Cardiomyocytes and mitochondria

Shouryadipta Ghosh, Kenneth Tran, Lea M D Delbridge, Anthony J R Hickey, Eric Hanssen, Edmund J Crampin, Vijay Rajagopal
Recent electron microscopy data have revealed that cardiac mitochondria are not arranged in crystalline columns but are organised with several mitochondria aggregated into columns of varying sizes often spanning the cell cross-section. This raises the question-how does the mitochondrial arrangement affect the metabolite distributions within cardiomyocytes and their impact on force dynamics? Here we employed finite element modelling of cardiac bioenergetics, using computational meshes derived from electron microscope images, to address this question...
December 5, 2018: PLoS Computational Biology
Ying Zhang, Yue Wang, Junnan Xu, Feng Tian, Shunying Hu, Yundai Chen, Zhenhong Fu
Optic atrophy 1 (OPA1)-related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1-related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial stress in the setting of cardiac ischemia reperfusion (I/R) injury. Our results indicated that OPA1, mitochondrial fusion and mitophagy were significantly repressed by I/R injury, accompanied by infarction area expansion, heart dysfunction, myocardial inflammation, and cardiomyocyte oxidative stress...
December 5, 2018: Journal of Pineal Research
Yu-Zhen Li, Xu-Dong Wu, Xiu-Hua Liu, Pei-Feng Li
The rhythmic contraction of cardiomyocytes consumes a lot of energy. 90% of ATP in cardiomyocytes is produced by mitochondria. Maintenance of a healthy population of mitochondria by mitophagy is critical for cardiomyocyte survival and normal function. Mitophagy refers to selective removal of damaged mitochondria by autophagy mechanism. The process of mitophagy must be restricted to dysfunctional mitochondria and maintained at a balanced level. Disruption in the balance inevitably leads to cardiomyocyte injury and dysfunction...
December 2, 2018: Acta Physiologica
Guibo Song, Mingjun Han, Zuhua Li, Xuedong Gan, Xiaowen Chen, Jie Yang, Sufang Dong, Ming Yan, Jun Wan, Yanggan Wang, Zhuliang Huang, Zhan Yin, Fang Zheng
The alpha regulator subunit B'' of protein phosphatase 2 (PPP2R3A), a regulatory subunit of protein phosphatase 2A (PP2A), was reported to present a special subcellular localization in cardiomyocytes and elevate in non-ischemia failing hearts. PPP2R3A has two transcriptions PR72 and PR130. PR72 acts as a negative regulator of the Wnt signaling cascade, while the Wnt signaling cascade plays a pivotal role in cardiac development. And PR130 was found to be involved in cardiac development of zebrafish in our previous study...
2018: PloS One
Julliane Vasconcelos Joviano-Santos, Artur Santos-Miranda, Ana Flávia Machado Botelho, Itamar Couto Guedes de Jesus, Jéssica Neves Andrade, Tatiane de Oliveira Barreto, Matheus Proença S Magalhães-Gomes, Priscila Aparecida Costa Valadão, Jader Dos Santos Cruz, Marília Martins Melo, Silvia Guatimosim, Cristina Guatimosim
Huntington's disease (HD) is a neurodegenerative genetic disorder. Although described as a brain pathology, there is evidence suggesting that defects in other systems can contribute to disease progression. In line with this, cardiovascular defects are a major cause of death in HD. To date, relatively little is known about the peripheral abnormalities associated with the disease. Here, we applied a range of assays to evaluate cardiac electro-mechanical properties in vivo, using a previously characterized mouse model of HD (BACHD), and in vitro, using cardiomyocytes isolated from the same mice...
November 19, 2018: FEBS Journal
Bin Zhang, Jingyi Zhang, Chenyang Zhang, Xuelian Zhang, Jingxue Ye, Shihuan Kuang, Guibo Sun, Xiaobo Sun
Diabetic cardiomyopathy (DCM) leads to heart failure and death in diabetic patients, no effective treatment is available. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and our previous studies have showed cardioprotective and neuroprotective effects of NGR1. However, its role in protecting against DCM remains unexplored. Herein, we examine potential effects of NGR1 on cardiac function of diabetic db/db mice and H9c2 cardiomyocytes treated by advanced glycation end products (AGEs)...
2018: Frontiers in Pharmacology
Akiyuki Nishimura, Tsukasa Shimauchi, Tomohiro Tanaka, Kakeru Shimoda, Takashi Toyama, Naoyuki Kitajima, Tatsuya Ishikawa, Naoya Shindo, Takuro Numaga-Tomita, Satoshi Yasuda, Yoji Sato, Koichiro Kuwahara, Yoshito Kumagai, Takaaki Akaike, Tomomi Ide, Akio Ojida, Yasuo Mori, Motohiro Nishida
Defective mitochondrial dynamics through aberrant interactions between mitochondria and actin cytoskeleton is increasingly recognized as a key determinant of cardiac fragility after myocardial infarction (MI). Dynamin-related protein 1 (Drp1), a mitochondrial fission-accelerating factor, is activated locally at the fission site through interactions with actin. Here, we report that the actin-binding protein filamin A acted as a guanine nucleotide exchange factor for Drp1 and mediated mitochondrial fission-associated myocardial senescence in mice after MI...
November 13, 2018: Science Signaling
Michael J Boyer, Satoru Eguchi
The interplay between the actin cytoskeleton and mitochondria has been implicated in cell and tissue homeostasis and physiological function. In this issue of Science Signaling , Nishimura et al. demonstrate that inhibiting the interaction of filamin A, an actin cytoskeleton regulator, with Drp1, a modulator of mitochondrial dynamics, attenuates mitochondrial hyperfission and cardiomyocyte senescence after myocardial infarction.
November 13, 2018: Science Signaling
Swati Paliwal, Rituparna Chaudhuri, Anurag Agrawal, Sujata Mohanty
BACKGROUND: Recent studies have demonstrated mesenchymal stem cells (MSCs) as effective mitochondrial donors with therapeutic success in multiple experimental models of human disease. MSCs obtained from different tissue sources such as bone marrow (BM), adipose (AD), dental pulp (DP), and Wharton's jelly (WJ) are routinely used in clinical trials with no known study of their mitochondrial donor capacity. Here, we show for the first time that MSCs derived from different tissue sources have different mitochondrial donor properties and that this is correlated with their intrinsic respiratory states...
November 8, 2018: Stem Cell Research & Therapy
Nicolai M Doliba, Andriy M Babsky, Mary D Osbakken
Cardiovascular complications are the major cause of mortality and morbidity in diabetic patients. The changes in myocardial structure and function associated with diabetes are collectively called diabetic cardiomyopathy. Numerous molecular mechanisms have been proposed that could contribute to the development of diabetic cardiomyopathy and have been studied in various animal models of type 1 or type 2 diabetes. The current review focuses on the role of sodium (Na+ ) in diabetic cardiomyopathy and provides unique data on the linkage between Na+ flux and energy metabolism, studied with non-invasive 23 Na, and 31 P-NMR spectroscopy, polarography, and mass spectroscopy...
2018: Frontiers in Physiology
E A Ostrakhovitch, S Tabibzadeh
There are numerous theories of aging, a process which still seems inevitable. Aging leads to cancer and multi-systemic disorders as well as chronic diseases including those that impair the functions of endothelial cells, kidney and lung. Decline in age- associated cellular functions leads to neurodegeneration and cognitive decline that affect the quality of life. Accumulation of damage, mutations, metabolic changes, failure in cellular energy production and clearance of altered proteins over the lifetime, and hyperhomocysteinemia, ultimately result in tissue degeneration...
November 1, 2018: Ageing Research Reviews
Bei-Lei Liu, Mian Cheng, Shan Hu, Shun Wang, Le Wang, Xin Tu, Cong-Xin Huang, Hong Jiang, Gang Wu
BACKGROUND AND PURPOSE: Our previous studies have shown that Src homology 2 (SH2) B adaptor protein 1 (SH2B1) plays an important role in cardiac hypertrophy, but the specific mechanism remains to be studied. Through bioinformatics and related research, it is found that miR-14 2-3 p is closely related to SH2B1. Exploring the relationship between miR-14 2-3 p and gene SH2B1 expression is beneficial for the treatment of cardiac hypertrophy. SH2B1 is a key factor regulating energy metabolism, mitochondria are the main organelles of energy metabolism and cardiac hypertrophy are closely related to mitochondrial dysfunction...
December 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Chowdhury S Abdullah, Shafiul Alam, Richa Aishwarya, Sumitra Miriyala, Manikandan Panchatcharam, Mohammad Alfrad Nobel Bhuiyan, Jonette M Peretik, A Wayne Orr, Jeanne James, Hanna Osinska, Jeffrey Robbins, John N Lorenz, Md Shenuarin Bhuiyan
Background The Sigma 1 receptor (Sigmar1) functions as an interorganelle signaling molecule and elicits cytoprotective functions. The presence of Sigmar1 in the heart was first reported on the basis of a ligand-binding assay, and all studies to date have been limited to pharmacological approaches using less-selective ligands for Sigmar1. However, the physiological function of cardiac Sigmar1 remains unknown. We investigated the physiological function of Sigmar1 in regulating cardiac hemodynamics using the Sigmar1 knockout mouse (Sigmar1-/- )...
October 16, 2018: Journal of the American Heart Association
Ruilin Yang, Patrick Ernst, Jiajia Song, Xiaoguang M Liu, Sabine Huke, Shuxin Wang, Jianyi Jay Zhang, Lufang Zhou
Background Oxidative stress-mediated Ca2+ /calmodulin-dependent protein kinase II (Ca MKII) phosphorylation of cardiac ion channels has emerged as a critical contributor to arrhythmogenesis in cardiac pathology. However, the link between mitochondrial-derived reactive oxygen species (md ROS ) and increased Ca MKII activity in the context of cardiac arrhythmias has not been fully elucidated and is difficult to establish experimentally. Methods and Results We hypothesize that pathological md ROS can cause erratic action potentials through the oxidation-dependent Ca MKII activation pathway...
August 7, 2018: Journal of the American Heart Association
Loren P Thompson, Ling Chen, Brian M Polster, Gerard Pinkas, Hong Song
Adverse intrauterine conditions cause fetal growth restriction and increase the risk of adult cardiovascular disease. We hypothesize that intrauterine hypoxia impairs fetal heart function, is sustained after birth, and manifest as both cardiac and mitochondrial dysfunction in offspring guinea pigs. METHODS: Pregnant guinea pigs (GPs) were exposed to either 10.5%O2 (HPX) at 50d gestation (term =65d) or normoxia (NMX) for the duration of the pregnancy. Pups were allowed to deliver vaginally and raised in a NMX environment...
October 26, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Dongjian Hu, Annet Linders, Abir Yamak, Cláudia Correia, Jan David Kijlstra, Arman Garakani, Ling Xiao, David J Milan, Peter van der Meer, Margarida Serra, Paula M Alves, Ibrahim J Domian
RATIONALE: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a readily available, robustly reproducible, and physiologically appropriate human cell source for cardiac disease modeling, drug discovery, and toxicity screenings in vitro. However, unlike adult myocardial cells in vivo, hPSC-CMs cultured in vitro maintain an immature metabolic phenotype, where majority of ATP is produced through aerobic glycolysis instead of oxidative phosphorylation in the mitochondria. Little is known about the underlying signaling pathways controlling hPSC-CMs' metabolic and functional maturation...
October 12, 2018: Circulation Research
George H Kunkel, Christopher J Kunkel, Hazel Ozuna, Irina Miralda, Suresh C Tyagi
Heart failure (HF) is a functional lack of myocardial performance due to a loss of molecular control over increases in calcium and ROS, resulting in proteolytic degradative advances and cardiac remodeling. Mitochondria are the molecular powerhouse of cells, shifting the sphere of cardiomyocyte stability and performance. Functional mitochondria rely on the molecular abilities of safety factors such as TFAM to maintain physiological parameters. Mitochondrial transcription factor A (TFAM) creates a mitochondrial nucleoid structure around mtDNA, protecting it from mutation, inhibiting NFAT (ROS activator/hypertrophic stimulator), and transcriptionally activates Serca2a to decrease calcium mishandling...
October 23, 2018: Molecular and Cellular Biochemistry
Siwen Li, Hongjing Zhao, Yu Wang, Yizhi Shao, Juanjuan Liu, Mingwei Xing
Arsenic-based drugs as food additive were used in poultry. However, excessive arsenic exposure can disturb myocardial cell metabolism, which results in the inhibition of growth and development of chickens. Since disordered mitochondria influences cardiac physiology and pathology, a better understanding of the mechanisms modulating cardiomyocyte mitochondria process is critical for identifying the potent detoxication targets under arsenic exposure in chickens. Male Hy-line chickens (1-day-old) were fed either a basal diet or an arsenic trioxide (As2O3)-supplemented diet containing 7...
October 18, 2018: Poultry Science
Parisa Samangouei, Gustavo E Crespo-Avilan, Hector Cabrera-Fuentes, Sauri Hernández-Reséndiz, Nur Izzah Ismail, Khairunnisa Binte Katwadi, William A Boisvert, Derek J Hausenloy
Acute myocardial infarction (AMI) and the heart failure (HF) that often follows are among the leading causes of death and disability worldwide. As such novel therapies are needed to reduce myocardial infarct (MI) size, and preserve left ventricular (LV) systolic function in order to reduce the propensity for HF following AMI. Mitochondria are dynamic organelles that can undergo morphological changes by two opposing processes, mitochondrial fusion and fission. Changes in mitochondrial morphology and turnover are a vital part of maintaining mitochondrial health, DNA stability, energy production, calcium homeostasis, cellular division, and differentiation, and disturbances in the balance of fusion and fission can predispose to mitochondrial dysfunction and cell death...
August 2018: Conditioning medicine
Weijian Hang, Benhong He, Jiehui Chen, Liangtao Xia, Bing Wen, Tao Liang, Xu Wang, Qianying Zhang, Yue Wu, Qingjie Chen, Juan Chen
Background: Type II diabetes (T2D)-induced cardiomyocyte hypertrophy is closely linked to the impairment of mitochondrial function. Berberine has been shown to be a promising effect for hypoglycemia in T2D models. High glucose-induced cardiomyocyte hypertrophy in vitro has been reported. The present study investigated the protective effect and the underlying mechanism of berberine on high glucose-induced H9C2 cell line. Methods: High glucose-induced H9C2 cell line was used to mimic the hyperglycemia resulting in cardiomyocyte hypertrophy...
2018: Frontiers in Pharmacology
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