MitoKATP channels promote the proliferation of hypoxic human pulmonary artery smooth muscle cells via the ROS/HIF/miR‑210/ISCU signaling pathway

Hu,Hongling; Ding,Yu; Wang,Yang; Geng,Shuang; Liu,Jue; He,Jinrong; Lu,Yang; Li,Xueying; Yuan,Mingli; Zhu,Shan; Zhao,Su

doi:10.3892/etm.2017.5322

MitoKATP channels promote the proliferation of hypoxic human pulmonary artery smooth muscle cells via the ROS/HIF/miR‑210/ISCU signaling pathway

Authors:
- Hongling Hu
- Yu Ding
- Yang Wang
- Shuang Geng
- Jue Liu
- Jinrong He
- Yang Lu
- Xueying Li
- Mingli Yuan
- Shan Zhu
- Su Zhao
View Affiliations

Affiliations: Department of Respiratory Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China, Key Laboratory for Molecular Diagnosis of Hubei, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China, Department of Clinical Pharmacy, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China
Published online on: October 17, 2017 https://doi.org/10.3892/etm.2017.5322
Pages: 6105-6112

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Previous results have indicated that mitochondrial ATP‑sensitive potassium (mitoKATP) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of mitoKATP channels on cell proliferation in response to hypoxia remains unknown. mitoKATP channel opening results in a collapse of mitochondrial membrane potential and generation of mitochondrial reactive oxygen species (ROS). As hypoxia‑inducible factor‑1α (HIF‑1α) is a critical oxygen sensor and major transcriptional regulator of the hypoxic adaptive response, the current study assessed whether mitoKATP opening contributes to the chronic proliferation of human PASMCs (hPASMCs) in collaboration with HIF‑1α and its downstream targets under hypoxic conditions. The present study demonstrated that there was crosstalk between mitoKATP channels and HIF‑1α signaling in PASMCs under hypoxic conditions. The results suggest that mitoKATP channels are involved in the proliferation of PASMCs during hypoxia through upregulation of the ROS/HIF/microRNA‑210/iron‑sulfur cluster protein signaling pathway.

View Figures

View References

1	Blok IM, van Riel ACMJ, van Dijk APJ, Mulder BJM and Bouma BJ: From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: Further improvement? Int J Cardiol. 227:51–52. 2017. View Article : Google Scholar : PubMed/NCBI
2	Ryan JJ and Archer SL: Emerging concepts in the molecular basis of pulmonary arterial hypertension (PAH): Part I: Metabolic plasticity and mitochondrial dynamics in the pulmonary circulation and right ventricle in pulmonary arterial hypertension. Circulation. 131:1691–1702. 2015. View Article : Google Scholar : PubMed/NCBI
3	Frumkin LR: The pharmacological treatment of pulmonary arterial hypertension. Pharmacol Rev. 64:583–620. 2012. View Article : Google Scholar : PubMed/NCBI
4	Ibe JC, Zhou Q, Chen T, Tang H, Yuan JX, Raj JU and Zhou G: Adenosine monophosphate-activated protein kinase is required for pulmonary artery smooth muscle cell survival and the development of hypoxic pulmonary hypertension. Am J Respir Cell Mol Biol. 49:609–618. 2013. View Article : Google Scholar : PubMed/NCBI
5	Vanden Hoek TL, Becker LB, Shao Z, Li C and Schumacker PT: Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem. 273:18092–18098. 1998. View Article : Google Scholar : PubMed/NCBI
6	Pain T, Yang XM, Critz SD, Yue Y, Nakano A, Liu GS, Heusch G, Cohen MV and Downey JM: Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res. 87:460–466. 2000. View Article : Google Scholar : PubMed/NCBI
7	Han J, Kim N, Park J, Seog DH, Joo H and Kim E: Opening of mitochondrial ATP-sensitive potassium channels evokes oxygen radical generation in rabbit heart slices. J Biochem. 131:721–727. 2002. View Article : Google Scholar : PubMed/NCBI
8	Teramoto N: Physiological roles of ATP-sensitive K+ channels in smooth muscle. J Physiol. 572:617–624. 2006. View Article : Google Scholar : PubMed/NCBI
9	Samavati L, Monick MM, Sanlioglu S, Buettner GR, Oberley LW and Hunninghake GW: Mitochondrial K(ATP) channel openers activate the ERK kinase by an oxidant-dependent mechanism. Am J Physiol Cell Physiol. 283:C273–C281. 2002. View Article : Google Scholar : PubMed/NCBI
10	Zhao JP, Guo Z, Zhou ZG, Chen J, Hu HL, Wang T and Zhang ZX: Effect of opening of mitochondrial ATP-sensitive K(+) channels on the expression of hypoxia inducible factor-1alpha and cell proliferation in pulmonary arterial smooth muscle cells of rats. Sheng Li Xue Bao. 59:157–162. 2007.(In Chinese). PubMed/NCBI
11	Hu HL, Zhang ZX, Chen CS, Cai C, Zhao JP and Wang X: Effects of mitochondrial potassium channel and membrane potential on hypoxic human pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol. 42:661–666. 2010. View Article : Google Scholar : PubMed/NCBI
12	Wang Y, Liu Y, Chen J, Tang MJ, Zhang SL, Wei LN, Li CH and Wei DB: Restriction-ligation-free (RLF) cloning: A high-throughput cloning method by in vivo homologous recombination of two PCR products. Genet Mol Res. 14:12306–12315. 2015. View Article : Google Scholar : PubMed/NCBI
13	Jin Z, Sun T, Xia X, Wei Q, Song Y, Han Q, Chen Q, Hu J and Zhang J: Optimized expression, purification of herpes B virus gD protein in Escherichia coli, and production of its monoclonal antibodies. Jundishapur J Microbiol. 9:e321832016. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Lu YY, Chen TS, Qu JL, Pan WL, Sun L and Wei XB: Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. J Biomed Sci. 16:162009. View Article : Google Scholar : PubMed/NCBI
16	Zhang J, Jin Z, Sun T, Jiang Y, Han Q, Song Y, Chen Q and Xia X: Prokaryotic expression, purification and polyclonal antibody production of a truncated recombinant rabies virus L protein. Iranian J Biotechnol. 13:18–24. 2015. View Article : Google Scholar
17	Suski JM, Lebiedzinska M, Bonora M, Pinton P, Duszynski J and Wieckowski MR: Relation between mitochondrial membrane potential and ROS formation. Methods Mol Biol. 810:183–205. 2012. View Article : Google Scholar : PubMed/NCBI
18	Wang Y and Wei L, Wei D, Li X, Xu L and Wei L: Testis-specific lactate dehydrogenase (LDH-C4) in skeletal muscle enhances a pika's sprint-running capacity in hypoxic environment. Int J Environ Res Public Health. 12:9218–9236. 2015. View Article : Google Scholar : PubMed/NCBI
19	Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li JL, et al: MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU. PLoS One. 5:e103452010. View Article : Google Scholar : PubMed/NCBI
20	Lee DC, Romero R, Kim JS, Tarca AL, Montenegro D, Pineles BL, Kim E, Lee J, Kim SY, Draghici S, et al: miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: Siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies. Am J Pathol. 179:590–602. 2011. View Article : Google Scholar : PubMed/NCBI
21	Rouault TA and Tong WH: Iron-sulfur cluster biogenesis and human disease. Trends Genet. 24:398–407. 2008. View Article : Google Scholar : PubMed/NCBI
22	Zhang H, Sun K, Ding J, Xu H, Zhu L, Zhang K, Li X and Sun W: Harmine induces apoptosis and inhibits tumor cell proliferation, migration and invasion through down-regulation of cyclooxygenase-2 expression in gastric cancer. Phytomedicine. 21:348–355. 2014. View Article : Google Scholar : PubMed/NCBI
23	Noma A: ATP-regulated K+ channels in cardiac muscle. Nature. 305:147–148. 1983. View Article : Google Scholar : PubMed/NCBI
24	Costa AD, Quinlan CL, Andrukhiv A, West IC, Jabůrek M and Garlid KD: The direct physiological effects of mitoK(ATP) opening on heart mitochondria. Am J Physiol Heart Circ Physiol. 290:H406–H415. 2006. View Article : Google Scholar : PubMed/NCBI
25	Nilakantan V, Liang H, Mortensen J, Taylor E and Johnson CP: Variable effects of the mitoK(ATP) channel modulators diazoxide and 5-HD in ATP-depleted renal epithelial cells. Mol Cell Biochem. 335:211–222. 2010. View Article : Google Scholar : PubMed/NCBI
26	Teshima Y, Akao M, Li RA, Chong TH, Baumgartner WA, Johnston MV and Marbán E: Mitochondrial ATP-sensitive potassium channel activation protects cerebellar granule neurons from apoptosis induced by oxidative stress. Stroke. 34:1796–1802. 2003. View Article : Google Scholar : PubMed/NCBI
27	Cao C, Healey S, Amaral A, Lee-Couture A, Wan S, Kouttab N, Chu W and Wan Y: ATP-sensitive potassium channel: A novel target for protection against UV-induced human skin cell damage. J Cell Physiol. 212:252–263. 2007. View Article : Google Scholar : PubMed/NCBI
28	Malinska D, Mirandola SR and Kunz WS: Mitochondrial potassium channels and reactive oxygen species. FEBS Lett. 584:2043–2048. 2010. View Article : Google Scholar : PubMed/NCBI
29	Brunelle JK, Bell EL, Quesada NM, Vercauteren K, Tiranti V, Zeviani M, Scarpulla RC and Chandel NS: Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab. 1:409–414. 2005. View Article : Google Scholar : PubMed/NCBI
30	Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, Simon MC, Hammerling U and Schumacker PT: Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab. 1:401–408. 2005. View Article : Google Scholar : PubMed/NCBI
31	Simon MC: Mitochondrial reactive oxygen species are required for hypoxic HIF alpha stabilization. Adv Exp Med Biol. 588:165–170. 2006. View Article : Google Scholar : PubMed/NCBI
32	Semenza GL: Hydroxylation of HIF-1: Oxygen sensing at the molecular level. Physiology (Bethesda). 19:176–182. 2004. View Article : Google Scholar : PubMed/NCBI
33	Majmundar AJ, Wong WJ and Simon MC: Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 40:294–309. 2010. View Article : Google Scholar : PubMed/NCBI
34	Chavez A, Miranda LF, Pichiule P and Chavez JC: Mitochondria and hypoxia-induced gene expression mediated by hypoxia-inducible factors. Ann N Y Acad Sci. 1147:312–320. 2008. View Article : Google Scholar : PubMed/NCBI
35	Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER and Ratcliffe PJ: The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature. 399:271–275. 1999. View Article : Google Scholar : PubMed/NCBI
36	Chan SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL and Loscalzo J: MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 10:273–284. 2009. View Article : Google Scholar : PubMed/NCBI
37	Huang X, Le QT and Giaccia AJ: MiR-210-micromanager of the hypoxia pathway. Trends Mol Med. 16:230–237. 2010. View Article : Google Scholar : PubMed/NCBI
38	Chen Z, Li Y, Zhang H, Huang P and Luthra R: Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene. 29:4362–4368. 2010. View Article : Google Scholar : PubMed/NCBI