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Akt/PKB heart

Shuai Yang, Xinmei Zhao, Hui Xu, Fan Chen, Yitao Xu, Zhe Li, Daniel Sanchis, Liang Jin, Yubin Zhang, Junmei Ye
The AKT (protein kinase B, PKB) family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2(-/-)) mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism and apoptotic signaling pathway. Here, we show that AKT2 inhibition does not affect the development of cardiomyocytes but increases cell death during cardiomyocyte ischemia. Caspase-dependent apoptosis of both the extrinsic and intrinsic pathway was inactivated in cardiomyocytes with AKT2 inhibition during ischemia, while significant mitochondrial disruption was observed as well as intracytosolic translocation of cytochrome C (Cyto C) together with apoptosis-inducing factor (AIF) and endonuclease G (EndoG), both of which are proven to conduct DNA degradation in a range of cell death stimuli...
March 6, 2017: International Journal of Molecular Sciences
Ademola Adetokunbo Oyagbemi, Dirk Bester, Johan Esterhuyse, Ebenezer Olatunde Farombi
OBJECTIVE: The study was designed to investigate the ameliorative effect of Kolaviron (KV) on ischemic/reperfusion injury in experimental animal models. MATERIALS AND METHODS: Male Wistar rats were randomly divided into two groups: Group 1 received corn oil as a vehicle and rats in Group 2 were administered KV at 200 mg/kg for 4 weeks. The rats were fed with rat standard chow pellet and water administered ad libitum. After 4 weeks of KV administration, hearts were excised and mounted on the working heart perfusion system...
January 2017: Journal of Intercultural Ethnopharmacology
Ruduwaan Salie, Amanda Lochner, Dirk J Loubser
Exposure of the heart to 5 min global ischaemia (I) followed by 5 min reperfusion (R) (ischaemic preconditioning, IPC) or transient Beta 2-adrenergic receptor (B2-AR) stimulation with formoterol (B2PC), followed by 5 min washout before index ischaemia, elicits cardioprotection against subsequent sustained ischaemia. Since the washout period during preconditioning is essential for subsequent cardioprotection, the aim of this study was to investigate the involvement of protein kinase A (PKA), reactive oxygen species (ROS), extracellular signal-regulated kinase (ERK), PKB/Akt, p38 MAPK and c-jun N-terminal kinase (JNK) during this period...
January 24, 2017: Cardiovascular Therapeutics
Hsueh-Wei Yen, Hui-Li Lin, Chi-Long Hao, Fu-Chih Chen, Chun-Yun Chen, Jia-Hao Chen, Kuo-Ping Shen
To investigate using pre-germinated brown rice (PGBR) to treat metabolic syndrome, we fed one group of mice standard-regular-diet (SRD) for 20 weeks and another group of mice high-fat-diet (HFD) for 16 weeks. We subdivided them into HFD group and HFD + PGBR group whose dietary carbohydrate was replaced with PGBR for 4 weeks. The HFD group gained more weight, had higher blood pressure, heart rate, blood glucose and lipids, liver levels of TG, feces TG and bile acid, lower adipose levels of adipocytokine, lower skeletal muscle IR, IRS-1, IRS-2, PI3 K, Akt/PKB, GLUT-1, GLUT-4, GCK and PPAR-γ; higher liver SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α, and higher adipose SREBP-1, SCD-1, FAS, and lower adipose PPAR-α and adiponectin...
May 2017: Bioscience, Biotechnology, and Biochemistry
Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, María Esther Rubio-Ruiz
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hui Li, Yiqing Mao, Qun Zhang, Qing Han, Zhenming Man, Jingyu Zhang, Xi Wang, Ruobi Hu, Xuehui Zhang, David M Irwin, Gang Niu, Huanran Tan
ETHNOPHARMACOLOGICAL RELEVANCE: Using insects, such as the cockroach, for the treatment of disease has a long history in traditional Chinese medicine. Xinmailong (XML) Injection, a bioactive composite extracted from Periplaneta americana (a species of cockroach), shows reasonable protective effects against cardiovascular injury and was approved for the use in the treatment of cardiac dysfunction in 2006, yet its cardio protective mechanisms remain unclear. AIM: The present study aims to examine the protective effects of XML against epirubicin-induced cardiotoxicity in vivo and determine its underlying mechanisms...
November 4, 2016: Journal of Ethnopharmacology
Qianqian Liang, Baoyu Wang, Lingxia Pang, Youpei Wang, Meiqin Zheng, Qing Wang, Jingbin Yan, Jinzhong Xu
OBJECTIVES: Higher cellular reactive oxygen species (ROS) levels is important in reducing cellular energy charge (EC) by increasing the levels of key metabolic protein, and nitrosative modifications, and have been shown to damage the cardiac tissue of diabetic mice. However, the relation between energy production and heart function is unclear. MATERIALS AND METHODS: Streptozotocin (STZ, 150 mg/kg body weight) was injected intraperitoneally once to mice that had been fasted overnight for induction of diabetes...
January 2016: Iranian Journal of Basic Medical Sciences
Yun-tai Yao, Ding-hua Liu, Li-huan Li
OBJECTIVE: To examine whether the combination of anesthetic preconditioning and anesthetic postconditioning could elicit additional cardio-protection as compared to either anesthetic preconditioning or anesthetic postconditioning alone and its underlying mechanism. METHODS: Isolated rat hearts were randomized into one of four groups: CTRL group (30 min of ischemia followed by 120 min of reperfusion alone); SpreC group (3% sevoflurane preconditioning was administered for 15 min followed by 10 min of washout before ischemia); SpostC group (3% sevoflurane postconditioning was administered during the first 15 min of reperfusion after ischemia); SpreC+SpostC group (the protocols of SpreC and SpostC were combined)...
March 2016: Perfusion
Amy E Mendham, Rob Duffield, Aaron J Coutts, Frank Marino, Andriy Boyko, David J Bishop
INTRODUCTION: The present study investigated whether rugby small-sided games (SSG) could be an effective alternative to continuous stationary cycling (CYC) training at reducing clinical risk factors associated with the development of type 2 diabetes mellitus (T2DM). METHODS: Thirty-three middle-aged (48.6±6.6y), inactive men were randomized into a CYC (n=11), SSG (n=11), or control (CON, n=11) group. Participants trained 3d·wk(-1) for 8 weeks, while control participants maintained normal activity and dietary patterns...
2015: PloS One
Mei Peng, Xiaoping Yang
Diabetes, particularly type II diabetes, is a severe disease condition which affects human health worldwide, with a dramatically increasing trend in Asian countries including China. Currently, no efficient drugs other than those with observable side effects are available. Chromium complexes, with the most known representative chromium picolinate, have been listed as one of most attractive health supplements to attenuate this disease condition in western countries. Recent efforts have been made to develop new chromium complexes with novel ligands...
May 2015: Journal of Inorganic Biochemistry
X-J Qian, X-L Li, X Xu, X Wang, Q-T Feng, C-J Yang
The phosphoinositide-3 kinase (PI3K) - phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade plays a critical role in cardiovascular development and tumor genesis. But the role of PDK1 in the microenvironment of heart and tumor remains unknown. To clarify the effects of PDK1 on tissue microenvironment in vivo, here, we created α-SMA-Cre-mediated excision of PDK1 mice. And the mice were injected subcutaneously with Lewis lung carcinoma (LLC) cells. We found PDK1-deficient mice had post-natal praecox dilated cardiomyopathy, decelerated tumor growth and severe tumor metastasis...
April 2015: Pathologie-biologie
Sang-Bing Ong, Andrew R Hall, Rachel K Dongworth, Siavash Kalkhoran, Aswin Pyakurel, Luca Scorrano, Derek J Hausenloy
The mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; p< 0...
March 2015: Thrombosis and Haemostasis
Ruduwaan Salie, Barbara Huisamen, Amanda Lochner
BACKGROUND: Although obesity is still considered a risk factor in the development of cardiovascular disorders, recent studies suggested that it may also be associated with reduced morbidity and mortality, the so-called "obesity paradox". Experimental data on the impact of diabetes, obesity and insulin resistance on myocardial ischaemia/reperfusion injury are controversial. Similar conflicting data have been reported regarding the effects of ischaemic preconditioning on ischaemia/reperfusion injury in hearts from such animals...
2014: Cardiovascular Diabetology
Frederic Nduhirabandi, Barbara Huisamen, Hans Strijdom, Dee Blackhurst, Amanda Lochner
Chronic melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI). However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity/insulin resistance remains unknown. Herein, we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control and diet-induced obese Wistar rats (fed a high calorie diet for 20 wk) were each subdivided into three groups receiving drinking water with or without melatonin (4 mg/kg/day) for the last 6 or 3 wk of experimentation...
October 2014: Journal of Pineal Research
Yunshan Cao, Lichan Tao, Shutong Shen, Junjie Xiao, Hang Wu, Beibei Li, Xiangqi Wu, Wen Luo, Qi Xiao, Xiaoshan Hu, Hailang Liu, Junwei Nie, Shuangshuang Lu, Baiyin Yuan, Zhonglin Han, Bo Xiao, Zhongzhou Yang, Xinli Li
Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias...
December 13, 2013: International Journal of Molecular Sciences
Vikram Prasad, John N Lorenz, Marian L Miller, Kanimozhi Vairamani, Michelle L Nieman, Yigang Wang, Gary E Shull
Acute inhibition of the NHE1 Na(+)/H(+) exchanger protects against ischemia-reperfusion injury and chronic inhibition attenuates development of cardiac hypertrophy and failure. To determine the cardiac effects of chronic inhibition of NHE1 under non-pathological conditions we used NHE1-null mice as a model of long-term NHE1 inhibition. Cardiovascular performance was relatively normal in Nhe1(-/-) mice although cardiac contractility and relaxation were slightly improved in mutant mice of the FVB/N background...
December 2013: Journal of Molecular and Cellular Cardiology
Tanner M Fullmer, Shaobo Pei, Yi Zhu, Crystal Sloan, Robert Manzanares, Brandon Henrie, Karla M Pires, James E Cox, E Dale Abel, Sihem Boudina
It is believed that the diabetic myocardium is refractory to cardioprotection by ischemic preconditioning (IPC) mainly because of impaired insulin signaling to phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB or Akt). However, human as well as animal studies have clearly showed that the hearts of type 2 diabetic humans and animals may exhibit increased signaling through PI3K-Akt but yet are resistant to cardioprotection by IPC or ischemic post-conditioning. Therefore, this study was designed to determine whether activation of insulin signaling prior to IPC is detrimental for cardioprotection and to assess the role of insulin receptors (IRs) and Akt in mediating this effect...
November 2013: Journal of Molecular and Cellular Cardiology
Guo-guang Wang, Wei Li, Xiao-hua Lu, Xue Zhao, Lei Xu
AIM: To investigate cardioprotective effect of taurine in diabetic rats. METHODS: Male Sprague-Dawley rats were assigned randomly into four groups of 15 rats: control group, control+taurine group, streptozotocin (STZ) group, and STZ + taurine group. Rats in STZ and STZ+ taurine groups were treated by a single injection of STZ (70 mg kg-1, intraperitoneally) dissolved in 0.01 M citrate buffer (pH 4.5) for induction of diabetes, and rats in control and control+taurine groups were treated with the same volume citrate buffer...
April 2013: Croatian Medical Journal
B Huisamen, C George, D Dietrich, S Genade
AIM: Obesity and type 2 diabetes present with two debilitating complications, namely, hypertension and heart disease. The dried and ground pods of Prosopis glandulosa (commonly known as the Honey mesquite tree) which is part of the Fabaceae (or legume) family are currently marketed in South Africa as a food supplement with blood glucose-stabilising and anti-hypertensive properties. We previously determined its hypoglycaemic effects, and in the current study we determined the efficacy of P glandulosa as anti-hypertensive agent and its myocardial protective ability...
March 2013: Cardiovascular Journal of Africa
Bénédicte Demeulder, Elham Zarrinpashneh, Audrey Ginion, Benoit Viollet, Louis Hue, Mark H Rider, Jean-Louis Vanoverschelde, Christophe Beauloye, Sandrine Horman, Luc Bertrand
Eukaryotic elongation factor 2 (eEF-2) and mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K) signaling pathways control protein synthesis and are inhibited during myocardial ischemia. Intracellular acidosis and AMP-activated protein kinase (AMPK) activation, both occurring during ischemia, have been proposed to participate in this inhibition. We evaluated the contribution of AMPKα2, the main cardiac AMPK catalytic subunit isoform, in eEF2 and mTOR-p70S6K regulation using AMPKα2 KO mice...
June 2013: Biochimica et Biophysica Acta
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