Browse > Article
http://dx.doi.org/10.5483/BMBRep.2016.49.4.193

miR-185 inhibits endoplasmic reticulum stress-induced apoptosis by targeting Na+/H+ exchanger-1 in the heart  

Kim, Jin Ock (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))
Kwon, Eun Jeong (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))
Song, Dong Woo (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))
Lee, Jong Sub (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))
Kim, Do Han (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))
Publication Information
BMB Reports / v.49, no.4, 2016 , pp. 208-213 More about this Journal
Abstract
Prolonged ER stress (ERS) can be associated with the induction of apoptotic cell death in various heart diseases. In this study, we searched for microRNAs affecting ERS in the heart using in silico and in vitro methods. We found that miR-185 directly targets the 3′-untranslated region of Na+/H+ exchanger-1 (NHE-1), a protein involved in ERS. Cardiomyocyte ERS-triggered apoptosis induced by 100 ng/ml tunicamycin (TM) or 1 μM thapsigargin (TG), ERS inducers, was significantly reduced by miR-185 overexpression. Protein expression of pro-apoptotic markers such as CCAAT/enhancer-binding protein homologous protein (CHOP) and cleaved-caspase-3 was also markedly reduced by miR-185 in a dose-dependent manner. Cariporide (20 μM), a pharmacological inhibitor of NHE-1, also attenuated ERS-induced apoptosis in cardiomyocytes and CHOP protein expression, suggesting that NHE-1 plays an important role in ERS-associated apoptosis in cardiomyocytes. Collectively, the present results demonstrate that miR-185 is involved in cardio-protection against ERS-mediated apoptotic cell death.
Keywords
Cariporide; Caspase-3; CHOP; microRNA; Unfolded protein response;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Ron D and Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein resonse. Nat Rev Mol Cell Biol 8, 519-529   DOI
2 Groenendyk J, Agellon LB and Michalak M (2013) Coping with endoplasmic reticulum stress in the cardiovascular system. Annu Rev Physiol 75, 49-67   DOI
3 Ryoo HD (2015) Drosophila as a model for unfolded protein response research. BMB Rep 48, 445-453   DOI
4 Arduíno DM, Raquel Esteves A, Filipa Domingues A et al (2009) ER-mediated stress induces mitochondrial-dependent caspases activation in NT2 neuron-like cells. BMB Rep 42, 719-724   DOI
5 Groenendyk J, Sreenivasaiah PK, Kim DH, Agellon LB and Michalak M (2010) Biology of endoplasmic reticulum stress in the heart. Circ Res 107, 1185-1197   DOI
6 Valencia-Sanchez MA, Liu J, Hannon GJ and Parker R (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20, 515-524   DOI
7 Leite-Moreira AM, Lourenço AP, Falcão-Pires I and Leite-Moreira AF (2013) Pivotal role of microRNAs in cardiac physiology and heart failure. Drug Discov Today 18, 1243-1249   DOI
8 Chakrabarti S, Hoque AN and Karmazyn M (1997) A rapid ischemia-induced apoptosis in isolated rat hearts and its attenuation by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide). J Mol Cell Cardiol 29, 3169-3174   DOI
9 Varga Z V, Zvara A, Faragó N et al (2014) MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning: protectomiRs. Am J Physiol Heart Circ Physiol 307, H216-H227   DOI
10 He S, Liu P, Jian Z et al (2013) MiR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway. Biochem Biophys Res Commun 441, 763-769   DOI
11 Nakamura TY, Iwata Y, Arai Y, Komamura K and Wakabayashi S (2008) Activation of Na+/H+ exchanger 1 is sufficient to generate Ca2+ signals that induce cardiac hypertrophy and heart failure. Circ Res 103, 891-899   DOI
12 Gumina RJ, Mizumura T, Beier N, Schelling P, Schultz JJ and Gross GJ (1998) A new sodium/hydrogen exchange inhibitor, EMD 85131, limits infarct size in dogs when administered before or after coronary artery occlusion. J Pharmacol Exp Ther 286, 175-183
13 Knight DR, Smith AH, Flynn DM et al (2001) A novel sodium-hydrogen exchanger isoform-1 inhibitor, zoniporide, reduces ischemic myocardial injury in vitro and in vivo. J Pharmacol Exp Ther 297, 254-259
14 Alvarez B V and Villa-Abrille MC (2013) Mitochondrial NHE1: a newly identified target to prevent heart disease. Front Physiol 4, 152   DOI
15 Kim JO, Song DW, Kwon EJ et al (2015) miR-185 plays an Anti-Hypertrophic Role in the Heart via Multiple Targets in the Calcium-Signaling Pathways. PLoS One 10, e0122509   DOI
16 Lindholm D, Wootz H and Korhonen L (2006) ER stress and neurodegenerative diseases. Cell Death Differ 13, 385-392   DOI
17 Cook AR, Bardswell SC, Pretheshan S et al (2009) Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: a role for ER stress?. J Mol Cell Cardiol 46, 225-233   DOI
18 Chhabra R, Dubey R and Saini N (2011) Gene expression profiling indicate role of ER stress in miR-23a~27a~24-2 cluster induced apoptosis in HEK293T cells. RNA Biol 8, 648-664   DOI
19 Okada K, Minamino T, Tsukamoto Y et al (2004) Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis. Circulation 110, 705-712   DOI
20 Ma Y and Hendershot LM (2004) The role of the unfolded protein response in tumour development: friend or foe?. Nat Rev Cancer 4, 966-977   DOI
21 Yang F, Zhang L, Wang F et al (2011) Modulation of the unfolded protein response is the core of microRNA-122-involved sensitivity to chemotherapy in hepatocellular carcinoma. Neoplasia 13, 590-600   DOI
22 Cingolani HE and Ennis IL (2007) Sodium-hydrogen exchanger, cardiac overload, and myocardial hypertrophy. Circulation 115, 1090-1100   DOI
23 Karki P and Fliegel L (2010) Overexpression of the NHE1 isoform of the Na+/H+ exchanger causes elevated apoptosis in isolated cardiomyocytes after hypoxia/reoxygenation challenge. Mol Cell Biochem 338, 47-57   DOI
24 S. Engelhardt (2002) Inhibition of Na+-H+ exchange prevents hypertrophy, fibrosis, and heart failure in beta1-adrenergic receptor transgenic mice. Circ Res 90, 814-819   DOI
25 Garciarena CD, Caldiz CI, Correa MV et al (2008) Na+/H+ exchanger-1 inhibitors decrease myocardial superoxide production via direct mitochondrial action. J Appl Physiol 105, 1706-1713   DOI
26 Maron BJ, Ferrans VJ and Roberts WC (1975) Myocardial ultrastructure in patients with chronic aortic valve disease. Am J Cardiol 35, 725-739   DOI
27 Javadov S, Choi A, Rajapurohitam V, Zeidan A, Basnakian AG and Karmazyn M (2008) NHE-1 inhibition-induced cardioprotection against ischaemia/reperfusion is associated with attenuation of the mitochondrial permeability transition. Cardiovasc Res 77, 416-424   DOI
28 Teshima Y, Akao M, Jones SP and Marbán E (2003) Cariporide (HOE642), a selective Na+-H+ exchange inhibitor, inhibits the mitochondrial death pathway. Circulation 108, 2275-2281   DOI
29 Von Harsdorf R, Li PF and Dietz R (1999) Signaling pathways in reactive oxygen species induced cardiomyocyte apoptosis. Circulation 99, 2934-2941   DOI
30 Park CS, Cha H, Kwon EJ, Sreenivasaiah PK and Kim DH (2012) The chemical chaperone 4-phenylbutyric acid attenuates pressure-overload cardiac hypertrophy by alleviating endoplasmic reticulum stress. Biochem Biophys Res Commun 421, 578-584   DOI
31 Backs J, Song K, Bezprozvannaya S, Chang S and Olson EN (2006) CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest 116, 1853-1864   DOI
32 Eckstein LA, Van Quill KR, Bui SK, Uusitalo MS and O’Brien JM (2005) Cyclosporin A inhibits calcineurin/nuclear factor of activated T-cells signaling and induces apoptosis in retinoblastoma cells. Investig Ophthalmol Vis Sci 46, 782-790   DOI
33 Matsuda T, Arakawa N, Takuma K et al (2001) SEA0400, a novel and selective inhibitorof the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. J Pharmacol Exp Ther 298, 249-256