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Takuro Tobina, Yukari Mori, Yukiko Doi, Fuki Nakayama, Akira Kiyonaga, Hiroaki Tanaka
Muscle peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1)α gene expression is influenced by the Gly482Ser gene polymorphism, which is a candidate genetic risk factor for diabetes mellitus and obesity. This study investigated the effects of PGC-1 gene Gly482Ser polymorphisms on alterations in glucose and lipid metabolism induced by exercise training. A 12-week intervention study was performed for 119 participants who were more than 65 years of age and completed exercise training at lactate threshold intensity...
October 3, 2016: Journal of Physiological Sciences: JPS
Chi-Jing Choong, Hideki Mochizuki
Parkinson's disease (PD) presents a relative selective localization of pathology to substantia nigra and well-defined motor symptoms caused by dopaminergic degeneration that makes it an ideal target for gene therapy. Parallel progress in viral vector systems enables the delivery of therapeutic genes directly into brain with reasonable safety along with sustained transgene expression. To date, gene therapy for PD that has reached clinical trial evaluation is mainly based on symptomatic approach that involves enzyme replacement strategy and restorative approach that depends on the addition of neurotrophic factors...
September 16, 2016: Journal of Neural Transmission
Xiaowan Wang, Hailong Li, Shinghua Ding
We previously demonstrated that Pre-B-cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD(+) biosynthesis pathway, plays a brain and neuronal protective role in ischemic stroke. In this study, we further investigated the mechanism of its neuroprotective effect after ischemia in the primary cultured mouse cortical neurons. Using apoptotic cell death assay, fluorescent imaging, molecular biology, mitochondrial biogenesis measurements and Western blotting analysis, our results show that the overexpression of PBEF in neurons can significantly promote neuronal survival, reduce the translocation of apoptosis inducing factor (AIF) from mitochondria to nuclei and inhibit the activation of capase-3 after glutamate-induced excitotoxicity...
2016: Scientific Reports
A P Türkmen, S Kaplan, A Aksoy, Bz Altunkaynak, Kk Yurt, E Elibol, C Çokluk, Me Onger
This study was aimed at evaluating the potential effects of acute subdural hematoma (ASDH) and diclofenac sodium (DS) therapy following ASDH on the rat hippocampus. Twenty-four male Sprague Dawley rats were used and divided into four groups. 0.1 ml of non-heparinized autologous blood from the tail vein of the animals in the non-treatment group (NTG) and treatment group (TG) was injected into the subdural space. The TG received intramuscular diclofenac sodium at a 15 mg/kg dose daily from the postoperative second hour to the seventh day after the operation...
2016: Folia Neuropathologica
Shu-Fen Han, Jun Jiao, Wei Zhang, Jia-Ying Xu, Weiguo Zhang, Chun-Ling Fu, Li-Qiang Qin
OBJECTIVE: Dietary fiber consumption is associated with reduced risk for the development of noncommunicable diseases. The aim of the present study was to evaluate the effects of cereal dietary fiber on the levels of proteins involved in lipolysis and thermogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT) of C57 BL/6 J mice fed a high-fat diet (HFD). METHODS: Male C57BL/6 J mice were fed normal chow diet (Chow), HFD, HFD plus oat fiber (H-oat), or HFD plus wheat bran fiber (H-wheat) for 24 wk...
June 2, 2016: Nutrition
Christine Mölzer, Marlies Wallner, Carina Kern, Anela Tosevska, Ursula Schwarz, Rene Zadnikar, Daniel Doberer, Rodrig Marculescu, Karl-Heinz Wagner
Energy metabolism, involving the ATP-dependent AMPK-PgC-Ppar pathway impacts metabolic health immensely, in that its impairment can lead to obesity, giving rise to disease. Based on observations that individuals with Gilbert's syndrome (GS; UGT1A1(*)28 promoter mutation) are generally lighter, leaner and healthier than controls, specific inter-group differences in the AMPK pathway regulation were explored. Therefore, a case-control study involving 120 fasted, healthy, age- and gender matched subjects with/without GS, was conducted...
2016: Scientific Reports
Shailendra P Singh, Joseph Schragenheim, Jian Cao, John R Falck, Nader G Abraham, Lars Bellner
BACKGROUND/OBJECTIVES: Obesity is a risk factor in the development of type 2 diabetes mellitus (DM2), which is associated with increased morbidity and mortality, predominantly as a result of cardiovascular complications. Increased adiposity is a systemic condition characterized by increased oxidative stress (ROS), increased inflammation, inhibition of anti-oxidant genes such as HO-1 and increased degradation of epoxyeicosatrienoic acids (EETs). We previously demonstrated that EETs attenuate mitochondrial ROS...
September 2016: Prostaglandins & Other Lipid Mediators
Kathryn F Cunningham, Gyda C Beeson, Craig C Beeson, Paul J McDermott
UNLABELLED: Estrogen-related Receptors (ERR) are members of the steroid hormone receptor superfamily of transcription factors that regulate expression of genes required for energy metabolism including mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation. While ERRα and EPPγ isoforms are known to share a wide array of target genes in the adult myocardium, the function of ERRβ has not been characterized in cardiomyocytes. The purpose of this study was to determine the role of ERRβ in regulating energy metabolism in adult cardiomyocytes in primary culture...
2016: American Journal of Cardiovascular Disease
Zhen Li, Xi Liu, Lu Wang, Yan Wang, Chuang Du, Siyuan Xu, Yucheng Zhang, Chunhong Wang, Chengfeng Yang
The lead-induced toxic effect on mitochondria in Sertoli cells is not well studied and the underlying mechanism is poorly understood. Here we reported the potential role of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and multidrug resistance protein 1 (MRP1) in lead acetate-induced mitochondrial toxicity in mouse testicular Sertoli cells TM4 line. We found that lead acetate treatment significantly reduced the expression level of PGC-1α, but increased the level of MRP1 in mitochondria of TM4 cells...
April 29, 2016: Toxicology
Jie Li, Xiao-Yong Geng, Xiao-Liang Cong
Increasing evidences support that PGC-1α participates in regulating endothelial homeostasis, in part by mediating endothelial nitric oxide (NO) synthase (eNOS) activity and NO production. However, the molecular mechanisms by which PGC-1α regulates eNOS activity are not completely understood. In the present study, we investigated the effects of PGC-1α on eNOS dysfunction and further explore the underlying mechanisms. The results showed that PGC-1α expression was downregulated after AngiotensinII (AngII) treatment and paralleled with the decreased NO generation in human aortic endothelial cells...
August 2016: Vascular Pharmacology
Manasi S Shah, Michael Brownlee
The clinical correlations linking diabetes mellitus with accelerated atherosclerosis, cardiomyopathy, and increased post-myocardial infarction fatality rates are increasingly understood in mechanistic terms. The multiple mechanisms discussed in this review seem to share a common element: prolonged increases in reactive oxygen species (ROS) production in diabetic cardiovascular cells. Intracellular hyperglycemia causes excessive ROS production. This activates nuclear poly(ADP-ribose) polymerase, which inhibits GAPDH, shunting early glycolytic intermediates into pathogenic signaling pathways...
May 27, 2016: Circulation Research
Ana Isabel Padrão, Ana Cristina Corrêa Figueira, Ana Rocha-Faustino, Adelina Gama, Maria Margarida Loureiro, Maria João Neuparth, Daniel Moreira-Gonçalves, Rui Vitorino, Francisco Amado, Lúcio Lara Santos, Paula A Oliveira, José Alberto Duarte, Rita Ferreira
AIM: Exercise training has been suggested as a non-pharmacological approach to prevent skeletal muscle wasting and improve muscle function in cancer cachexia. However, little is known about the molecular mechanisms underlying such beneficial effect. In the present study we aimed to, firstly, examine the contribution of TWEAK signalling to cancer-induced skeletal muscle wasting and, secondly, evaluate whether long-term exercise alters TWEAK signalling and prevents muscle wasting. METHODS: Female Sprague-Dawley rats were randomly assigned to control and exercise groups...
May 26, 2016: Acta Physiologica
Samuel G Impey, Kelly M Hammond, Sam O Shepherd, Adam P Sharples, Claire Stewart, Marie Limb, Kenneth Smith, Andrew Philp, Stewart Jeromson, D Lee Hamilton, Graeme L Close, James P Morton
Using an amalgamation of previously studied "train-low" paradigms, we tested the effects of reduced carbohydrate (CHO) but high leucine availability on cell-signaling responses associated with exercise-induced regulation of mitochondrial biogenesis and muscle protein synthesis (MPS). In a repeated-measures crossover design, 11 males completed an exhaustive cycling protocol with high CHO availability before, during, and after exercise (HIGH) or alternatively, low CHO but high protein (leucine enriched) availability (LOW + LEU)...
May 2016: Physiological Reports
Maayan Waldman, Lars Bellner, Luca Vanella, Joseph Schragenheim, Komal Sodhi, Shailendra P Singh, Daohong Lin, Anand Lakhkar, Jiangwei Li, Edith Hochhauser, Michael Arad, Zbigniew Darzynkiewicz, Atallah Kappas, Nader G Abraham
Epoxyeicosatrienoic acid (EET) contributes to browning of white adipose stem cells to ameliorate obesity/diabetes and insulin resistance. In the current study, we show that EET altered preadipocyte function, enhanced peroxisome proliferation-activated receptor γ coactivator α (PGC-1α) expression, and increased mitochondrial function in the 3T3-L1 preadipocyte subjected to adipogenesis. Cells treated with EET resulted in an increase, P < 0.05, in PGC-1α and a decrease in mitochondria-derived ROS (MitoSox), P < 0...
July 15, 2016: Stem Cells and Development
Guo-Ying Miao, Xin Zhou, Xin Zhang, Yi Xie, Chao Sun, Yang Liu, Lu Gan, Hong Zhang
The effects of carbon-ion irradiation on cancer cell telomere function have not been comprehensively studied. In our previous report cancer cells with telomere dysfunction were more sensitive to carbon-ion irradiation, but the underlying mechanisms remained unclear. Here we found that telomerase activity was suppressed by carbon-ion irradiation via hTERT down-regulation. Inhibition of telomere activity by MST-312 further increased cancer cell radiosensitivity to carbon-ion radiation. hTERT suppression caused by either carbon-ion irradiation or MST-312 impaired mitochondrial function, as indicated by decreased membrane potential, mtDNA copy number, mitochondrial mass, total ATP levels and elevated reactive oxygen species (ROS)...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Kwang Sik Suh, Suk Chon, Eun Mi Choi
Methylglyoxal (MG), a reactive sugar-derived metabolite, exerts harmful effects by inducing oxidative stress, which aggravates a series of diabetic complications, including osteoporosis. The present study was performed to examine the effects of luteolin, a dietary polyphenolic flavonoid, on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. Pretreatment of MC3T3-E1 osteoblastic cells with luteolin prevented MG-induced cell death and production of tumor necrosis factor-alpha, intracellular reactive oxygen species, mitochondrial superoxide, and cardiolipin peroxidation...
May 24, 2016: Cytotechnology
Yu Kitaoka, Kohei Takeda, Yuki Tamura, Hideo Hatta
To examine the potential role of lactate as a signalling molecule in skeletal muscle, we performed global gene expression analysis of the mouse gastrocnemius muscle, 3 h after lactate administration using the Affymetrix GeneChip system (Affymetrix, Santa Clara, Calif., USA). Among the top 15 genes with the largest fold change, increased expression of Ppargc1a, Pdk4, and Ucp3 was confirmed using real-time quantitative polymerase chain reaction. Our findings suggest that lactate serves as a signal for upregulating genes related to mitochondrial function...
June 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Hye Jeong Yang, Min Jung Kim, Dae Young Kwon, Bo Reum Moon, A Reum Kim, Suna Kang, Sunmin Park
BACKGROUND: Artemisia princeps Pamp (APP), Leonurus japonicas Houtt (LJH), and Gardenia jasminoides Ellis fruit (GJE) have been traditionally used in East Asia to treat women's diseases related to reproductive system. They may attenuate the deterioration of energy, lipid, glucose and bone metabolism by estrogen deficiency. The present study explored the combination of APP, LJH, and GJE to overcome the symptoms of estrogen deficiency and the mechanism was explored. METHODS: Ovariectomized (OVX) rats were divided into five groups and fed high-fat diets supplemented with 2 % dextrin (control), 2 % APP, 2 % APP + LJH (15:5), APP + LJH + GJE (10:5:5) or 17β-estradiol (30 μg/kg bw/day) for 8 weeks...
2016: BMC Complementary and Alternative Medicine
Kohei Tanaka, Minoru Tanaka, Junya Takegaki, Hidemi Fujino
Cachexia is a complex metabolic syndrome associated with underlying chronic diseases and is characterized by the overexpression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), which impair muscle oxidative metabolism. We hypothesized that electrical stimulation (ES) would prevent decrement in muscle oxidative metabolism by suppressing the phosphorylation of p38 MAPK, a critical regulator of inflammatory response. Therefore, the purpose of the present study was to verify the effects of ES on inflammatory-induced decrement of oxidative metabolism in mice tibialis anterior muscles...
June 2016: Acta Histochemica
Wenju Li, Xiaoli Li, Bin Wang, Yan Chen, Aiping Xiao, Di Zeng, Dongbo Ou, Song Yan, Wei Li, Qiangsun Zheng
Diabetic cardiomyopathy increases the risk for the development of heart failure independent of coronary artery disease and hypertension. Either type 1 or type 2 diabetes is often accompanied by varying degrees of hyperglycemia, which has been proven to induce myocardial apoptosis in animal models. Recently, a novel small molecule, ZLN005, has been reported to show antidiabetic efficacy in a mouse model, possibly by induction of PGC-1α expression. In this study, we investigated whether ZLN005 protects cardiomyocytes against high glucose-induced cytotoxicity and the mechanisms involved...
July 1, 2016: Experimental Cell Research
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