低氧诱导因子-1在调控骨骼肌缺氧时能量代谢发生适应性变化的机制研究进展

doi:10.16098/j.issn.0529-1356.2017.02.021

摘要/Abstract

摘要：

低氧诱导因子-1(HIF-1) 是一种调控组织细胞氧稳态的关键性核转录因子，广泛存在于哺乳动物和人体内，其表达和活性受到细胞氧浓度的严密调控。它能在生理性和病理性缺氧缺血的情况下，通过调控细胞能量代谢、血管发生、红细胞生成、细胞生存、细胞增殖和凋亡等生物学效应，使细胞适应低氧环境得以生存或者走向凋亡。本文中我们主要概述了HIF-1的结构功能，及其在缺氧时调控骨骼肌能量代谢方面发生适应性变化的机制及研究进展。

关键词: 缺氧, 低氧诱导因子-1, 骨骼肌, 能量代谢

Abstract:

Hypoxia-inducible factor1 (HIF-1) is a key nuclear transcription factor that regulates the oxygen homeostasis of tissue cells and widely exists in both mammals and humans. The expression and activity of HIF-1 are tightly regulated by cellular oxygen concentration. It can regulate the biological effects of cellular energy metabolism, angiogenesis, erythropoiesis, cell survival, cell proliferation and apoptosis in the physiological and pathological hypoxic-ischemic condition, so that the cells can adapt to the hypoxic environment to survive, or to apoptosis. This paper reviewed the structure and function of HIF-1 and the recent progress on the study of the mechanism of energy metabolism of HIF-1-driven skeletal muscle adaptations to hypoxia.

Key words: Hypoxia, Hypoxia-inducible factor 1, Skeletal muscle, Energy metabolism

宋亚琼周播江. 低氧诱导因子-1在调控骨骼肌缺氧时能量代谢发生适应性变化的机制研究进展[J]. 解剖学报, 2017, 48(2): 236-240.

SONG Ya-qiong ZHOU Bo-jiang. Recent progress on the mechanism of energy metabolism of hypoxia-inducible factor 1-driven skeletal muscle adaptations to hypoxia[J]. Acta Anatomica Sinica, 2017, 48(2): 236-240.

参考文献

［1］Xing YQ, Xu J, Li L, et al. Advances in structure, regulation and target genes of hypoxia inducible factor (HIF-1) ［J］. Chinese Journal of Laboratory Diagnosis, 2011,15(1):177-179.(in Chinese)
邢英琦, 徐静, 李琳, 等. 缺氧诱导因子(HIF-1)的结构、调节与靶基因研究进展［J］.中国实验诊断学,2011,15(1):177-179.
［2］Favier FB, Britto FA, Freyssenet DG, et al. HIF-1-driven skeletal muscle adaptations to chronic hypoxia: molecular insights into muscle physiology［J］. Cell Mol Life Sci, 2015, 72(24): 4681-4696.
［3］Wang GL, Jiang BH, Rue EA, et al. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension［J］. Proc Natl Acad Sci USA, 1995, 92(12): 5510-5514.
［4］Wang XT, Liu PY, Tang JB. PDGF gene therapy enhances expression of VEGF and bFGF genes and activates the NF-κB gene in signal pathways in ischemic flaps［J］. Plast Reconstr Surg, 2006, 117(1): 129-137.
［5］Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress［J］. Mol cell, 2010, 40(2): 294-309.
［6］Patel SA, Simon MC. Biology of hypoxia-inducible factor-2α in development and disease［J］. Cell Death Differ, 2008, 15(4): 628-634.
［7］Loboda A, Jozkowicz A, Dulak J. HIF-1 and HIF-2 transcription factors—similar but not identical［J］. Mol cells, 2010, 29(5): 435-442.
［8］Lisy K, Peet DJ. Turn me on: regulating HIF transcriptional activity［J］. Cell Death Differ, 2008, 15(4): 642-649.
［9］Kuzmanov A, Wielockx B, Rezaei M, et al. Overexpression of factor inhibiting HIF-1 enhances vessel maturation and tumor growth via platelet-derived growth factor-C［J］. Int J Cancer, 2012, 131(5): E603-E613.
［10］Semenza GL. Hypoxia-inducible factor 1 and cardiovascular disease［J］. Annu Rev Physiol, 2014, 76: 39-56.
［11］Semenza GL. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy［J］. Trends Pharmacol Sci, 2012, 33(4): 207-214.
［12］Levy NS, Levy AP. Adapting to Hypoxia: Lessons from Vascular Endothelial Growth Factor［M］. Anoxia: Springer Netherlands, 2012: 113-128.
［13］Chepelev NL, Willmore WG. Regulation of iron pathways in response to hypoxia［J］. Free Radic Biol Med, 2011, 50(6): 645-666.
［14］Zhang WJ, Wang T, Xiao Y. Progress in copper regulation of hypoxia inducible factor 1 transcriptional activity ［J］. Progress in Physiological Sciences, 2016, 47(2): 119-123. (in Chinese)
张文菁, 王韬, 肖颖, 等. 铜调控低氧诱导因子1转录活性的研究进展［J］. 生理科学进展, 2016, 47(2): 119-123.
［15］Manalo DJ, Rowan A, Lavoie T, et al. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1［J］. Blood, 2005, 105(2): 659-669.
［16］Semenza GL. HIF-1, O2, and the 3 PHDs: how animal cells signal hypoxia to the nucleus［J］. Cell, 2001, 107(1): 1-3.
［17］Semenza GL. HIF-1: upstream and downstream of cancer metabolism［J］. Curr Opin Genet Dev, 2010, 20(1): 51-56.
［18］Liu Y, Cui YG, Mao YD. Hypoxia-inducible factors and their roles in energy metabolism［J］.Journal of Medical Postgraduates,2014,（27）5: 542-545. (in Chinese)
柳宇, 崔毓桂, 冒韵东. 缺氧诱导因子在细胞能量代谢中的作用［J］. 医学研究生学报, 2014,（27）5: 542-545.
［19］De Palma S, Ripamonti M, Vigano A, et al. Metabolic modulation induced by chronic hypoxia in rats using a comparative proteomic analysis of skeletal muscle tissue［J］. J Proteome Res, 2007, 6(5): 1974-1984.
［20］Ullah MS, Davies AJ, Halestrap AP. The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1α-dependent mechanism［J］. J Biol Chem, 2006, 281(14): 9030-9037.
［21］Regnault TR, Zhao L, Chiu JS, et al. Peroxisome proliferator-activated receptor-β/δ,-γ agonists and resveratrol modulate hypoxia induced changes in nuclear receptor activators of muscle oxidative metabolism［J］. PPAR Res, 2010, 2010:129173.
［22］Slot IG, Schols AM, Vosse BA, et al. Hypoxia differentially regulates muscle oxidative fiber type and metabolism in a HIF-1α-dependent manner［J］. Cell Signal, 2014, 26(9): 1837-1845.
［23］Chaillou T, Koulmann N, Meunier A, et al. Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload［J］. Acta Physiol (Oxf), 2013, 209(4): 272-282.
［24］Band M, Joel A, Hernandez A, et al. Hypoxia-induced BNIP3 expression and mitophagy: in vivo comparison of the rat and the hypoxia-tolerant mole rat, Spalax ehrenbergi［J］. FASEB J, 2009, 23(7): 2327-2335.
［25］Gamboa JL, Garcia-Cazarin ML, Andrade FH. Chronic hypoxia increases insulin-stimulated glucose uptake in mouse soleus muscle［J］. Am J Physiol Regul Integr Comp Physiol, 2011, 300(1): R85-R91.
［26］De Theije CC, Langen RC, Lamers WH, et al. Distinct responses of protein turnover regulatory pathways in hypoxia-and semistarvation-induced muscle atrophy［J］. Am J Physiol Lung Cell Mol Physiol, 2013, 305(1): L82-L91.
［27］Bellot G, Garcia-Medina R, Gounon P, et al. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains［J］. Mol Cell Biol, 2009, 29(10): 2570-2581.
［28］Chen R, Dioum EM, Hogg RT, et al. Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner［J］. Biol Chem, 2011, 286(16): 13869-13878.
［29］Kume S, Uzu T, Horiike K, et al. Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney［J］. J Clin Invest, 2010, 120(4): 1043-1055.
［30］Lokireddy S, Wijesoma IW, Teng S, et al. The ubiquitin ligase mul1 induces mitophagy in skeletal muscle in response to muscle-wasting stimuli［J］. Cell Metab, 2012, 16(5): 613-624.
［31］Snyder GK, Farrelly C, Coelho JR. Adaptations in skeletal muscle capillarity following changes in oxygen supply and changes in oxygen demands［J］. Eur J Appl Physiol Occup Physiol, 1992, 65(2): 158-163.
［32］Niemi H, Honkonen K, Korpisalo P, et al. HIF-1α and HIF-2α induce angiogenesis and improve muscle energy recovery［J］. Eur J Clin Invest, 2014, 44(10): 989-999.
［33］Favier FB, Costes F, Defour A, et al. Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia［J］. Am J Physiol Regul Integr Comp Physiol, 2010, 298(6): R1659-R1666.
［34］Chaillou T, Koulmann N, Meunier A, et al. Ambient hypoxia enhances the loss of muscle mass after extensive injury［J］. Pflugers Arch, 2014, 466(3): 587-598.
［35］De Theije CC, Langen RC, Lamers WH, et al. Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy［J］. J Appl Physiol (1985), 2015, 118(2): 200-211.
［36］Arthur PG, Giles JJ, Wakeford CM. Protein synthesis during oxygen conformance and severe hypoxia in the mouse muscle cell line C2C12［J］. Biochim Biophys Acta, 2000, 1475(1): 83-89.
［37］Sakagami H, Makino Y, Mizumoto K, et al. Loss of HIF-1α impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells［J］. Am J Physiol Endocrinol Metab, 2014, 306(9): E1065-E1076.
［38］Bagnall J, Leedale J, Taylor SE, et al. Tight control of hypoxia-inducible factor-α transient dynamics is essential for cell survival in hypoxia［J］. J Biol Chem, 2014, 289(9): 5549-5564.

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