SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells

Li,Pengyun; Liu,Yan; Burns,Nana; Zhao,Ke-Seng; Song,Rui

doi:10.3892/ijmm.2017.2932

SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells

Authors:
- Pengyun Li
- Yan Liu
- Nana Burns
- Ke-Seng Zhao
- Rui Song
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Affiliations: Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Pharmacy, Henan Medical College, Zhengzhou, Henan 450046, P.R. China, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
Published online on: March 22, 2017 https://doi.org/10.3892/ijmm.2017.2932
Pages: 1127-1136
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although recent studies have reported that mitochondria are putative oxygen sensors underlying hypoxic pulmonary vasoconstriction, little is known concerning the sirtuin 1 (SIRT1)-mediated mitochondrial biogenesis regulatory program in pulmonary arteriolar smooth muscle cells (PASMCs) during hypoxia/reoxygenation (H/R). We investigated the epigenetic regulatory mechanism of mitochondrial biogenesis and function in human PASMCs during H/R. Human PASMCs were exposed to hypoxia of 24-48 h and reoxygenation of 24-48 h. The expression of SIRT1 was reduced in a time-dependent manner. Mitochondrial transcription factor A (TFAM) expression was increased during hypoxia and decreased during reoxygenation, while the release of TFAM was increased in a time-dependent manner. Lentiviral overexpression of SIRT1 preserved SIRT3 deacetylase activity in human PASMCs exposed to H/R. Knockdown of PGC-1α suppressed the effect of SIRT1 on SIRT3 activity. Knockdown of SIRT3 abrogated SIRT1-mediated deacetylation of cyclophilin D (CyPD). Notably, knockdown of SIRT3 or PGC-1α suppressed the incremental effect of SIRT1 on mitochondrial TFAM, mitochondrial DNA (mtDNA) content and cellular ATP levels. Importantly, polydatin restored SIRT1 levels in human PASMCs exposed to H/R. Knockdown of SIRT1 suppressed the effect of polydatin on mitochondrial TFAM, mtDNA content and cellular ATP levels. In conclusion, SIRT1 expression is decreased in human PASMCs during H/R. TFAM expression in mitochondria is reduced and the release of TFAM is increased by H/R. PGC-1α/SIRT3/CyPD mediates the protective effect of SIRT1 on expression and release of TFAM and mitochondrial biogenesis and function. Polydatin improves mitochondrial biogenesis and function by enhancing SIRT1 expression in hypoxic human PASMCs.

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1	Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, et al Global Initiative for Chronic Obstructive Lung Disease: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 176:532–555. 2007. View Article : Google Scholar : PubMed/NCBI
2	Gibson PG and Simpson JL: The overlap syndrome of asthma and COPD: What are its features and how important is it? Thorax. 64:728–735. 2009. View Article : Google Scholar : PubMed/NCBI
3	Evans AM, Hardie DG, Peers C and Mahmoud A: Hypoxic pulmonary vasoconstriction: Mechanisms of oxygen-sensing. Curr Opin Anaesthesiol. 24:13–20. 2011. View Article : Google Scholar :
4	Freund-Michel V, Khoyrattee N, Savineau JP, Muller B and Guibert C: Mitochondria: Roles in pulmonary hypertension. Int J Biochem Cell Biol. 55:93–97. 2014. View Article : Google Scholar : PubMed/NCBI
5	Kalogeris T, Baines CP, Krenz M and Korthuis RJ: Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 298:229–317. 2012. View Article : Google Scholar : PubMed/NCBI
6	Li P, Meng X, Bian H, Burns N, Zhao KS and Song R: Activation of sirtuin 1/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage. Oncotarget. 6:36998–37011. 2015.PubMed/NCBI
7	Powell RD, Swet JH, Kennedy KL, Huynh TT, McKillop IH and Evans SL: Resveratrol attenuates hypoxic injury in a primary hepatocyte model of hemorrhagic shock and resuscitation. J Trauma Acute Care Surg. 76:409–417. 2014. View Article : Google Scholar : PubMed/NCBI
8	Jian B, Yang S, Chaudry IH and Raju R: Resveratrol restores sirtuin 1 (SIRT1) activity and pyruvate dehydrogenase kinase 1 (PDK1) expression after hemorrhagic injury in a rat model. Mol Med. 20:10–16. 2014. View Article : Google Scholar : PubMed/NCBI
9	Jian B, Yang S, Chaudry IH and Raju R: Resveratrol improves cardiac contractility following trauma-hemorrhage by modulating Sirt1. Mol Med. 18:209–214. 2012. View Article : Google Scholar :
10	Waypa GB, Osborne SW, Marks JD, Berkelhamer SK, Kondapalli J and Schumacker PT: Sirtuin 3 deficiency does not augment hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol. 49:885–891. 2013. View Article : Google Scholar : PubMed/NCBI
11	Paulin R, Dromparis P, Sutendra G, Gurtu V, Zervopoulos S, Bowers L, Haromy A, Webster L, Provencher S, Bonnet S, et al: Sirtuin 3 deficiency is associated with inhibited mitochondrial function and pulmonary arterial hypertension in rodents and humans. Cell Metab. 20:827–839. 2014. View Article : Google Scholar : PubMed/NCBI
12	Menzies KJ and Hood DA: The role of SirT1 in muscle mitochondrial turnover. Mitochondrion. 12:5–13. 2012. View Article : Google Scholar
13	Kong X, Wang R, Xue Y, Liu X, Zhang H, Chen Y, Fang F and Chang Y: Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis. PLoS One. 5:e117072010. View Article : Google Scholar : PubMed/NCBI
14	Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, et al: Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 434:658–662. 2005. View Article : Google Scholar : PubMed/NCBI
15	Marzetti E, Calvani R, Cesari M, Buford TW, Lorenzi M, Behnke BJ and Leeuwenburgh C: Mitochondrial dysfunction and sarcopenia of aging: From signaling pathways to clinical trials. Int J Biochem Cell Biol. 45:2288–2301. 2013. View Article : Google Scholar : PubMed/NCBI
16	Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, Deutsch WA, Smith SR and Ravussin E; CALERIE Pennington Team: Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 4:e762007. View Article : Google Scholar : PubMed/NCBI
17	Chaung WW, Wu R, Ji Y, Dong W and Wang P: Mitochondrial transcription factor A is a proinflammatory mediator in hemorrhagic shock. Int J Mol Med. 30:199–203. 2012.PubMed/NCBI
18	Liu HB, Meng QH, Huang C, Wang JB and Liu XW: Nephroprotective effects of polydatin against ischemia/reperfusion injury: A role for the PI3K/Akt signal pathway. Oxid Med Cell Longev. 2015:3621582015. View Article : Google Scholar : PubMed/NCBI
19	Li XH, Gong X, Zhang L, Jiang R, Li HZ, Wu MJ and Wan JY: Protective effects of polydatin on septic lung injury in mice via upregulation of HO-1. Mediators Inflamm. 2013:3540872013. View Article : Google Scholar : PubMed/NCBI
20	Zeng Z, Yang Y, Dai X, Xu S, Li T, Zhang Q, Zhao KS and Chen Z: Polydatin ameliorates injury to the small intestine induced by hemorrhagic shock via SIRT3 activation-mediated mitochondrial protection. Expert Opin Ther Targets. 20:645–652. 2016. View Article : Google Scholar : PubMed/NCBI
21	Wang X, Song R, Chen Y, Zhao M and Zhao KS: Polydatin - a new mitochondria protector for acute severe hemorrhagic shock treatment. Expert Opin Investig Drugs. 22:169–179. 2013. View Article : Google Scholar
22	Li P, Wang X, Zhao M, Song R and Zhao KS: Polydatin protects hepatocytes against mitochondrial injury in acute severe hemorrhagic shock via SIRT1-SOD2 pathway. Expert Opin Ther Targets. 19:997–1010. 2015. View Article : Google Scholar : PubMed/NCBI
23	Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A and Sinclair DA: Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY). 2:914–923. 2010. View Article : Google Scholar
24	Becker RH, Sha S, Frick AD and Fountaine RJ: The effect of smoking cessation and subsequent resumption on absorption of inhaled insulin. Diabetes Care. 29:277–282. 2006. View Article : Google Scholar : PubMed/NCBI
25	Rajendrasozhan S, Yang SR, Kinnula VL and Rahman I: SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 177:861–870. 2008. View Article : Google Scholar : PubMed/NCBI
26	Yao H, Sundar IK, Huang Y, Gerloff J, Sellix MT, Sime PJ and Rahman I: Disruption of sirtuin 1-mediated control of circadian molecular clock and inflammation in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 53:782–792. 2015. View Article : Google Scholar : PubMed/NCBI
27	Hsu CP, Zhai P, Yamamoto T, Maejima Y, Matsushima S, Hariharan N, Shao D, Takagi H, Oka S and Sadoshima J: Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation. 122:2170–2182. 2010. View Article : Google Scholar : PubMed/NCBI
28	Cattelan A, Ceolotto G, Bova S, Albiero M, Kuppusamy M, De Martin S, Semplicini A, Fadini GP, de Kreutzenberg SV and Avogaro A: NAD(+)-dependent SIRT1 deactivation has a key role on ischemia-reperfusion-induced apoptosis. Vascul Pharmacol. 70:35–44. 2015. View Article : Google Scholar : PubMed/NCBI
29	Uittenbogaard M and Chiaramello A: Mitochondrial biogenesis: a therapeutic target for neurodevelopmental disorders and neurodegenerative diseases. Curr Pharm Des. 20:5574–5593. 2014. View Article : Google Scholar : PubMed/NCBI
30	Pisano A, Cerbelli B, Perli E, Pelullo M, Bargelli V, Preziuso C, Mancini M, He L, Bates MG, Lucena JR, et al: Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure. Cardiovasc Pathol. 25:103–112. 2016. View Article : Google Scholar : PubMed/NCBI
31	Lee D, Kim KY, Noh YH, Chai S, Lindsey JD, Ellisman MH, Weinreb RN and Ju WK: Brimonidine blocks glutamate excitotoxicity-induced oxidative stress and preserves mitochondrial transcription factor a in ischemic retinal injury. PLoS One. 7:e470982012. View Article : Google Scholar : PubMed/NCBI
32	Yin W, Signore AP, Iwai M, Cao G, Gao Y and Chen J: Rapidly increased neuronal mitochondrial biogenesis after hypoxic-ischemic brain injury. Stroke. 39:3057–3063. 2008. View Article : Google Scholar : PubMed/NCBI
33	Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS and Clayton DA: Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet. 18:231–236. 1998. View Article : Google Scholar : PubMed/NCBI
34	Hokari M, Kuroda S, Kinugawa S, Ide T, Tsutsui H and Iwasaki Y: Overexpression of mitochondrial transcription factor A (TFAM) ameliorates delayed neuronal death due to transient forebrain ischemia in mice. Neuropathology. 30:401–407. 2010. View Article : Google Scholar : PubMed/NCBI
35	Liang H and Ward WF: PGC-1alpha: A key regulator of energy metabolism. Adv Physiol Educ. 30:145–151. 2006. View Article : Google Scholar : PubMed/NCBI
36	Lehman JJ, Barger PM, Kovacs A, Saffitz JE, Medeiros DM and Kelly DP: Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 106:847–856. 2000. View Article : Google Scholar : PubMed/NCBI
37	Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, et al: Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 98:115–124. 1999. View Article : Google Scholar : PubMed/NCBI
38	Kim SY, Shim MS, Kim KY, Weinreb RN, Wheeler LA and Ju WK: Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury. Cell Death Dis. 5:e11052014. View Article : Google Scholar : PubMed/NCBI
39	Gomes AP, Price L, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, et al: Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 155:1624–1638. 2013. View Article : Google Scholar : PubMed/NCBI
40	Joo HY, Yun M, Jeong J, Park ER, Shin HJ, Woo SR, Jung JK, Kim YM, Park JJ, Kim J, et al: SIRT1 deacetylates and stabilizes hypoxia-inducible factor-1α (HIF-1α) via direct interactions during hypoxia. Biochem Biophys Res Commun. 462:294–300. 2015. View Article : Google Scholar : PubMed/NCBI
41	Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, et al: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 127:1109–1122. 2006. View Article : Google Scholar : PubMed/NCBI
42	Kwon SM, Park HG, Jun JK and Lee WL: Exercise, but not quercetin, ameliorates inflammation, mitochondrial biogenesis, and lipid metabolism in skeletal muscle after strenuous exercise by high-fat diet mice. J Exerc Nutrition Biochem. 18:51–60. 2014. View Article : Google Scholar
43	Higashida K, Kim SH, Jung SR, Asaka M, Holloszy JO and Han DH: Effects of resveratrol and SIRT1 on PGC-1α activity and mitochondrial biogenesis: A reevaluation. PLoS Biol. 11:e10016032013. View Article : Google Scholar