跳轉至內容
Merck
  • Negative regulation of HIF in skeletal muscle of elite endurance athletes: a tentative mechanism promoting oxidative metabolism.

Negative regulation of HIF in skeletal muscle of elite endurance athletes: a tentative mechanism promoting oxidative metabolism.

American journal of physiology. Regulatory, integrative and comparative physiology (2014-06-06)
M E Lindholm, H Fischer, L Poellinger, R S Johnson, T Gustafsson, C J Sundberg, H Rundqvist
摘要

The transcription factor hypoxia-inducible factor (HIF) has been suggested as a candidate for mediating training adaptation in skeletal muscle. However, recent evidence rather associates HIF attenuation with a trained phenotype. For example, a muscle-specific HIF deletion increases endurance performance, partly through decreased levels of pyruvate dehydrogenase kinase 1 (PDK-1). HIF activity is regulated on multiple levels: modulation of protein stability, transactivation capacity, and target gene availability. Prolyl hydroxylases (PHD1-3) induces HIF degradation, whereas factor-inhibiting HIF (FIH) and the histone deacetylase sirtuin-6 (SIRT6) repress its transcriptional activity. Together, these negative regulators introduce a mechanism for moderating HIF activity in vivo. We hypothesized that long-term training induces their expression. Negative regulators of HIF were explored by comparing skeletal muscle tissue from moderately active individuals (MA) with elite athletes (EA). In elite athletes, expression of the negative regulators PHD2 (MA 73.54 ± 9.54, EA 98.03 ± 6.58), FIH (MA 4.31 ± 0.25, EA 30.96 ± 7.99) and SIRT6 (MA 0.24 ± 0.07, EA 11.42 ± 2.22) were all significantly higher, whereas the response gene, PDK-1 was lower (MA 0.12 ± 0.03, EA 0.04 ± 0.01). Similar results were observed in a separate 6-wk training study. In vitro, activation of HIF in human primary muscle cell culture by PHD inactivation strongly induced PDK-1 (0.84 ± 0.12 vs 4.70 ± 0.63), providing evidence of a regulatory link between PHD activity and PDK-1 levels in a relevant model system. Citrate synthase activity, closely associated with aerobic exercise adaptation, increased upon PDK-1 silencing. We suggest that training-induced negative regulation of HIF mediates the attenuation of PDK-1 and contributes to skeletal muscle adaptation to exercise.

材料
產品編號
品牌
產品描述

Sigma-Aldrich
甘氨酸, ReagentPlus®, ≥99% (HPLC)
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, suitable for electrophoresis, ≥99%
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, BioUltra, for molecular biology, ≥99.0% (NT)
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
单克隆 抗-α-肌动蛋白(肌小节) 小鼠抗, clone EA-53, ascites fluid
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, ≥98.5%
庫存單位
包裝尺寸
供貨能力
價格
數量
SAFC
甘氨酸
庫存單位
包裝尺寸
供貨能力
價格
數量
USP
甘氨酸, United States Pharmacopeia (USP) Reference Standard
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, BioXtra, ≥99% (titration)
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
DMOG, ≥98% (HPLC)
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, 99%, FCC
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, ACS reagent, ≥98.5%
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, meets analytical specification of Ph. Eur., BP, USP, 99-101% (based on anhydrous substance)
庫存單位
包裝尺寸
供貨能力
價格
數量
Supelco
甘氨酸, Pharmaceutical Secondary Standard; Certified Reference Material
庫存單位
包裝尺寸
供貨能力
價格
數量
Supelco
甘氨酸, analytical standard, for nitrogen determination according to Kjeldahl method
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, puriss. p.a., reag. Ph. Eur., buffer substance, 99.7-101% (calc. to the dried substance)
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, Vetec, reagent grade, 98%
庫存單位
包裝尺寸
供貨能力
價格
數量
甘氨酸, European Pharmacopoeia (EP) Reference Standard
庫存單位
包裝尺寸
供貨能力
價格
數量
Supelco
甘氨酸, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
庫存單位
包裝尺寸
供貨能力
價格
數量
Sigma-Aldrich
甘氨酸, tested according to Ph. Eur.
庫存單位
包裝尺寸
供貨能力
價格
數量