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Mitochondrial creatine kinase

Xijun Liang, Lin Liu, Tingting Fu, Qian Zhou, Danxia Zhou, Liwei Xiao, Jing Liu, Yan Kong, Hui Xie, Fanchao Yi, Ling Lai, Rick B Vega, Daniel P Kelly, Steven R Smith, Zhenji Gan
Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and lactate, which are critical fuel metabolites of skeletal muscle particularly during exercise. However, the physiological relevance of LDH remains poorly understood. Here we show that Ldhb expression is induced by exercise in human muscle and negatively correlated with changes in intramuscular pH levels, a marker of lactate production, during isometric exercise. We found that the expression of Ldhb is regulated by exercise-induced peroxisome proliferator-activated receptor-g coactivator 1α (PGC-1α)...
October 13, 2016: Journal of Biological Chemistry
Qiang Li, Li Shen, Zhen Wang, Hai-Peng Jiang, Li-Xia Liu
OBJECTIVE: To determine the mechanism by which Tanshinone IIA (Tan IIA) relieves myocardial ischemia reperfusion injury (MIRI) in rats via the PI3K/Akt/mTOR signaling pathway. METHODS: Sprague-Dawley (SD) rats received an intravenous injection of Tan IIA and LY294002 and were divided into the sham, control (myocardial ischemia reperfusion), Tan-L (low-dose Tan IIA), Tan-H (high-dose Tan IIA), Tan-L+LY (low-dose Tan IIA+LY294002), Tan-H+LY (high-dose Tan IIA+LY294002) and LY (LY294002) groups...
September 16, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Neal J Dawson, Catherine M Ivy, Luis Alza, Rebecca Cheek, Julia M York, Beverly Chua, William K Milsom, Kevin G McCracken, Graham R Scott
Torrent ducks inhabit fast-flowing rivers in the Andes from sea level to altitudes up to 4,500 m. We examined the mitochondrial physiology that facilitates performance over this altitudinal cline by comparing the respiratory capacities of permeabilized fibers, the activities of 16 key metabolic enzymes, and the myoglobin content in muscles between high- and low-altitude populations of this species. Mitochondrial respiratory capacities (assessed using substrates of mitochondrial complexes I, II, and/or IV) were higher in highland ducks in the gastrocnemius muscle - the primary muscle used to support swimming and diving - but were similar between populations in the pectoralis muscle and the left ventricle...
September 12, 2016: Journal of Experimental Biology
Tomica Ambang, Joo-San Tan, Sheila Ong, Kum-Thong Wong, Khean-Jin Goh
Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for chronic hepatitis B infection. While raised serum creatine kinase is common, myopathy associated with telbivudine is rare. Reports on its myopathological features are few and immunohistochemical analyses of inflammatory cell infiltrates have not been previously described. We describe the clinical, myopathological and immunohistochemical features of four patients who developed myopathy after telbivudine therapy for chronic hepatitis B infection...
2016: PloS One
Marta Novotová, Bohumila Tarabová, Lucia Tylková, Renee Ventura-Clapier, Ivan Zahradník
Creatine kinase content, isoform distribution, and participation in energy transfer are muscle type specific. We analysed ultrastructural changes in slow muscle fibres of soleus due to invalidation of creatine kinase (CK) to reveal a difference in the remodelling strategy in comparison with fast muscle fibres of gastrocnemius published previously. We have employed the stereological method of vertical sections and electron microscopy of soleus muscles of wild type (WT) and CK-/- mice. The mitochondrial volume density was 1...
September 9, 2016: General Physiology and Biophysics
Niina Karro, Mervi Sepp, Svetlana Jugai, Martin Laasmaa, Marko Vendelin, Rikke Birkedal
Rainbow trout (Oncorhynchus mykiss) cardiomyocytes have a simple morphology with fewer membrane structures such as sarcoplasmic reticulum and t-tubules penetrating the cytosol. Despite this, intracellular ADP diffusion is restricted. Intriguingly, although diffusion is restricted, trout cardiomyocytes seem to lack the coupling between mitochondrial creatine kinase (CK) and respiration. Our aim was to study the distribution of diffusion restrictions in permeabilized trout cardiomyocytes and verify the role of CK...
August 13, 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Elda M Rueda, Jerry E Johnson, Anand Giddabasappa, Anand Swaroop, Matthew J Brooks, Irena Sigel, Shawnta Y Chaney, Donald A Fox
PURPOSE: The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases...
2016: Molecular Vision
Sebastian Müller, Miroslav Balaz, Patrik Stefanicka, Lukas Varga, Ez-Zoubir Amri, Jozef Ukropec, Bernd Wollscheid, Christian Wolfrum
Human brown adipose tissue (BAT) has become an attractive target to combat the current epidemical spread of obesity and its associated co-morbidities. Currently, information on its functional role is primarily derived from rodent studies. Here, we present the first comparative proteotype analysis of primary human brown adipose tissue versus adjacent white adipose tissue, which reveals significant quantitative differences in protein abundances and in turn differential functional capabilities. The majority of the 318 proteins with increased abundance in BAT are associated with mitochondrial metabolism and confirm the increased oxidative capacity...
2016: Scientific Reports
Francine R Ianiski, Virginia C Rech, Vivian S K Nishihira, Catiane B Alves, Matheus D Baldissera, Ethel A Wilhelm, Cristiane Luchese
Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-β or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam-loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol...
July 11, 2016: Anais da Academia Brasileira de Ciências
Paula M Miotto, Graham P Holloway
The transport of cytosolic adenosine diphosphate (ADP) into the mitochondria is a major control point in metabolic homeostasis, as ADP concentrations directly affect glycolytic flux and oxidative phosphorylation rates within mitochondria. A large contributor to the efficiency of this process is thought to involve phosphocreatine (PCr)/Creatine (Cr) shuttling through mitochondrial creatine kinase (Mi-CK), whereas the biological importance of alterations in Cr-independent ADP transport during exercise remains unknown...
September 15, 2016: Biochemical Journal
Jun Liu, Shuangmei Yang, Xiaoran Zhang, Guoze Liu, Xiuqin Yue
Isoflurane (ISO) protects the heart from hypoxia-reperfusion injury. However, the molecular mechanisms of ISO in oxygen-glucose deprivation (OGD)-induced H9c2 cardiomyocyte injury is yet to be understood. Using H9c2 cells cultured in vitro, we examined the cytotoxicity of different doses of ISO (0.7%, 1.4%, and 2.1%) to H9c2 cells and found that 2.1% ISO had significant toxicity to the cell. Thus, 1.4% ISO was selected for the subsequent experiments. ISO notably ameliorated cell viability loss, lactate dehydrogenase release, and creatine kinase activity of H9c2 cells that were treated with OGD...
2016: American Journal of Translational Research
Hongyan Li, Shanshan Zhang, Faliang Li, Lijie Qin
Increasing evidence suggests that inflammation and apoptosis are involved in the development of acute myocardial ischemia (AMI). Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) have recently been identified as key mediators of inflammatory responses. The aim of this study was to explore the specific role and the underlying regulatory mechanism of NLRX1 in myocardial ischemic injury. The results show that NLRX1, located in mitochondria, was significantly down-regulated in AMI tissues and hypoxia-induced H9c2 cells...
August 2016: Molecular Immunology
Paula M Miotto, Graham P Holloway
No abstract text is available yet for this article.
May 2016: Medicine and Science in Sports and Exercise
Rodrigo Binkowski de Andrade, Tanise Gemelli, Denise Bertin Rojas, Tomas Duk Hwa Kim, Ângela Zanatta, Felipe Schmitz, André Felipe Rodrigues, Angela T S Wyse, Moacir Wajner, Carlos Severo Dutra-Filho, Clovis Milton Duval Wannmacher
Sarcosine is an N-methyl derivative of the amino acid glycine, and its elevation in tissues and physiological fluids of patients with sarcosinemia could reflect a deficient pool size of activated 1-carbon units. Sarcosinemia is a rare inherited metabolic condition associated with mental retardation. In the present study, we investigated the acute effect of sarcosine and/or creatine plus pyruvate on some parameters of oxidative stress and energy metabolism in cerebral cortex homogenates of 21-day-old Wistar rats...
June 29, 2016: Molecular Neurobiology
Samar O El-Ganainy, Ahmed El-Mallah, Dina Abdallah, Mahmoud M Khattab, Mahmoud M Mohy El-Din, Aiman S El-Khatib
Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg)...
June 1, 2016: Toxicology
Daniel S Lark, Maria J Torres, Chien-Te Lin, Terence E Ryan, Ethan J Anderson, P Darrell Neufer
Oxidative phosphorylation (OXPHOS) efficiency, defined as the ATP-to-O ratio, is a critical feature of mitochondrial function that has been implicated in health, aging, and disease. To date, however, the methods to measure ATP/O have primarily relied on indirect approaches or entail parallel rather than simultaneous determination of ATP synthesis and O2 consumption rates. The purpose of this project was to develop and validate an approach to determine the ATP/O ratio in permeabilized fiber bundles (PmFBs) from simultaneous measures of ATP synthesis (JATP) and O2 consumption (JO2 ) rates in real time using a custom-designed apparatus...
August 1, 2016: American Journal of Physiology. Cell Physiology
Uwe Schlattner, Anna Klaus, Sacnicte Ramirez Rios, Rita Guzun, Laurence Kay, Malgorzata Tokarska-Schlattner
There is an increasing body of evidence for local circuits of ATP generation and consumption that are largely independent of global cellular ATP levels. These are mostly based on the formation of multiprotein(-lipid) complexes and diffusion limitations existing in cells at different levels of organization, e.g., due to the viscosity of the cytosolic medium, macromolecular crowding, multiple and bulky intracellular structures, or controlled permeability across membranes. Enzymes generating ATP or GTP are found associated with ATPases and GTPases enabling the direct fueling of these energy-dependent processes, and thereby implying that it is the local and not the global concentration of high-energy metabolites that is functionally relevant...
August 2016: Amino Acids
Xue Yanyan, Lin Duomao, Wang Zhaoqi, Yang Yanli, Cheng Yi, Ma Jun
OBJECTIVE: To compare the protective effect of different dose of penehyclidine hydrochloride (PHC) in rats with myocardial ischemia/reperfusion (I/R) injury. METHODS: Forty-eight healthy male Wistar rats were randomly divided into six groups (n = 8 each): sham group, sham + 1.0 mg/kg PHC group (sham + H-PHC group), I/R group, I/R + 0.1 mg/kg PHC preconditioning group (I/R + L-PHC group), I/R + 0.3 mg/kg PHC preconditioning group (I/R + M-PHC group), and I/R + 1...
December 2015: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Can Wei, Hongzhu Li, Yuehong Wang, Xue Peng, Hongjiang Shao, Hongxia Li, Shuzhi Bai, Changqing Xu
Myocardial infarction (MI) is associated with a high mortality rate, which is attributed to the effects of myocyte loss that occurs as a result of ischemia-induced cell death. Very few therapies can effectively prevent or delay the effects of ischemia. Polyamines (PAs) are polycations required for cell growth and division, and their use may prevent cell loss. The aim of this study was to investigate the relationship between hypoxia/ischemia (H/I)-induced cell apoptosis and PA metabolism and to investigate the ability of spermine to limit H/I injury in cardiomyocytes by blocking the mitochondrial apoptotic pathway...
August 2016: Experimental Biology and Medicine
Jian-Kui Du, Bin-Hai Cong, Qing Yu, He Wang, Long Wang, Chang-Nan Wang, Xiao-Lu Tang, Jian-Qiang Lu, Xiao-Yan Zhu, Xin Ni
Mitochondrial oxidative damage is critically involved in cardiac ischemia reperfusion (I/R) injury. MicroRNA-22 (miR-22) has been predicted to potentially target sirtuin-1 (Sirt1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), both of which are known to provide protection against mitochondrial oxidative injury. The present study aims to investigate whether miR-22 is involved in the regulation of cardiac I/R injury by regulation of mitochondrial function. We found that miR-22 level was significantly increased in rat hearts subjected to I/R injury, as compared with the sham group...
July 2016: Free Radical Biology & Medicine
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