Role of tRNA selenocysteine 1 associated protein 1 in the proliferation and apoptosis of cardiomyocyte‑like H9c2 cells

Li,Meng‑Di; Cheng,Wan‑Peng; Shi,Min‑Xia; Ge,Tang‑Dong; Zheng,Xiao‑Lin; Wu,Dong‑Yuan; Hu,Xiao‑Yan; Luo,Jin‑Cheng; Li,Feng‑Lan; Li,Hui

doi:10.3892/mmr.2016.6099

Role of tRNA selenocysteine 1 associated protein 1 in the proliferation and apoptosis of cardiomyocyte‑like H9c2 cells

Authors:
- Meng‑Di Li
- Wan‑Peng Cheng
- Min‑Xia Shi
- Tang‑Dong Ge
- Xiao‑Lin Zheng
- Dong‑Yuan Wu
- Xiao‑Yan Hu
- Jin‑Cheng Luo
- Feng‑Lan Li
- Hui Li
View Affiliations

Affiliations: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
Published online on: December 30, 2016 https://doi.org/10.3892/mmr.2016.6099
Pages: 988-994

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

Transfer RNA selenocysteine 1 associated protein 1 (Trnau1ap) serves an essential role in the synthesis of selenoproteins, which have critical functions in numerous biological processes. Selenium deficiency results in a variety of diseases, including cardiac disease. However, the mechanisms underlying myocardial injury induced by selenium deficiency remain unclear. The present study examined the effects of Trnau1ap under‑ and overexpression in cardiomyocyte‑like H9c2 cells, by transfection with small interfering RNA and an overexpression plasmid, respectively. Expression levels of glutathione peroxidase, thioredoxin reductase and selenoprotein K were decreased in Trnau1ap‑underexpressing cells, and increased in Trnau1ap‑overexpressing cells. Using MTT, proliferating cell nuclear antigen, annexin V and caspase‑3 activity assays, it was demonstrated that reducing Trnau1ap expression levels inhibited the proliferation of H9c2 cells and induced apoptosis. Conversely, increasing Trnau1ap expression levels promoted cell growth. Western blot analysis revealed that the phosphoinositide 3‑kinase/protein kinase B signaling pathway was activated in Trnau1ap‑underexpressing cells. Furthermore, the apoptotic pathway was activated in these cells, evidenced by relatively greater expression levels of B‑cell lymphoma (Bcl‑2)‑associated X protein and reduced expression levels of Bcl‑2. Taken together, these findings suggest that Trnau1ap serves a key role in the proliferation and apoptosis of H9c2 cells. The present study provides insight into the underlying mechanisms of myocardial injury induced by selenium deficiency.

View Figures

View References

1	Lu J and Holmgren A: Selenoproteins. J Biol Chem. 284:723–727. 2009. View Article : Google Scholar : PubMed/NCBI
2	Combs GF Jr: Biomarkers of selenium status. Nutrients. 7:2209–2236. 2015. View Article : Google Scholar : PubMed/NCBI
3	Rayman MP: Selenium and human health. Lancet. 379:1256–1268. 2012. View Article : Google Scholar : PubMed/NCBI
4	Mehdi Y, Hornick JL, Istasse L and Dufrasne I: Selenium in the environment, metabolism and involvement in body functions. Molecules. 18:3292–3311. 2013. View Article : Google Scholar : PubMed/NCBI
5	Turanov AA, Xu XM, Carlson BA, Yoo MH, Gladyshev VN and Hatfield DL: Biosynthesis of selenocysteine, the 21st amino acid in the genetic code, and a novel pathway for cysteine biosynthesis. Adv Nutr. 2:122–128. 2011. View Article : Google Scholar : PubMed/NCBI
6	Metanis N and Hilvert D: Natural and synthetic selenoproteins. Curr Opin Chem Biol. 22:27–34. 2014. View Article : Google Scholar : PubMed/NCBI
7	Huang Z, Rose AH and Hoffmann PR: The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 16:705–743. 2012. View Article : Google Scholar : PubMed/NCBI
8	Reeves MA and Hoffmann PR: The human selenoproteome: Recent insights into functions and regulation. Cell Mol Life Sci. 66:2457–2478. 2009. View Article : Google Scholar : PubMed/NCBI
9	Diamond AM: The subcellular location of selenoproteins and the impact on their function. Nutrients. 7:3938–3948. 2015. View Article : Google Scholar : PubMed/NCBI
10	Squires JE and Berry MJ: Eukaryotic selenoprotein synthesis: Mechanistic insight incorporating new factors and new functions for old factors. IUBMB Life. 60:232–235. 2008. View Article : Google Scholar : PubMed/NCBI
11	Ding F and Grabowski PJ: Identification of a protein component of a mammalian tRNA(Sec) complex implicated in the decoding of UGA as selenocysteine. RNA. 5:1561–1569. 1999. View Article : Google Scholar : PubMed/NCBI
12	Small-Howard A, Morozova N, Stoytcheva Z, Forry EP, Mansell JB, Harney JW, Carlson BA, Xu XM, Hatfield DL and Berry MJ: Supramolecular complexes mediate selenocysteine incorporation in vivo. Mol Cell Biol. 26:2337–2346. 2006. View Article : Google Scholar : PubMed/NCBI
13	Papp LV, Lu J, Holmgren A and Khanna KK: From selenium to selenoproteins: Synthesis, identity, and their role in human health. Antioxid Redox Signal. 9:775–806. 2007. View Article : Google Scholar : PubMed/NCBI
14	Xu XM, Mix H, Carlson BA, Grabowski PJ, Gladyshev VN, Berry MJ and Hatfield DL: Evidence for direct roles of two additional factors, SECp43 and soluble liver antigen, in the selenoprotein synthesis machinery. J Biol Chem. 280:41568–41575. 2005. View Article : Google Scholar : PubMed/NCBI
15	Oropeza-Moe M, Wisløff H and Bernhoft A: Selenium deficiency associated porcine and human cardiomyopathies. J Trace Elem Med Biol. 31:148–156. 2015. View Article : Google Scholar : PubMed/NCBI
16	Rose AH and Hoffmann PR: Selenoproteins and cardiovascular stress. Thromb Haemost. 113:494–504. 2015. View Article : Google Scholar : PubMed/NCBI
17	Cui J, Zhong R, Chu E, Zhang XF, Zhang WG, Fang CF, Dong Q, Li FL and Li H: Correlation between oxidative stress and L-type calcium channel expression in the ventricular myocardia of selenium-deficient mice. J Int Med Res. 40:1677–1687. 2012. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Method. 25:402–408. 2001. View Article : Google Scholar
19	Mahdi Y, Xu XM, Carlson BA, Fradejas N, Günter P, Braun D, Southon E, Tessarollo L, Hatfield DL and Schweizer U: Expression of selenoproteins is maintained in mice carrying mutations in SECp43, the tRNA selenocysteine 1 associated protein (Trnau1ap). PLoS One. 10:e01273492015. View Article : Google Scholar : PubMed/NCBI
20	Wang SC: PCNA: A silent housekeeper or a potential therapeutic target? Trends Pharmacol Sci. 35:178–186. 2014. View Article : Google Scholar : PubMed/NCBI
21	Moldovan GL, Pfander B and Jentsch S: PCNA, the maestro of the replication fork. Cell. 129:665–679. 2007. View Article : Google Scholar : PubMed/NCBI
22	Ip C, Thompson HJ and Ganther HE: Selenium modulation of cell proliferation and cell cycle biomarkers in normal and premalignant cells of the rat mammary gland. Cancer Epidemiol Biomarkers Prev. 9:49–54. 2000.PubMed/NCBI
23	Chen JH, Tsou TC, Chiu IM and Chou CC: Proliferation inhibition, DNA damage, and cell-cycle arrest of human astrocytoma cells after acrylamide exposure. Chem Res Toxicol. 23:1449–1458. 2010. View Article : Google Scholar : PubMed/NCBI
24	Zeng H: Selenium as an essential micronutrient: Roles in cell cycle and apoptosis. Molecules. 14:1263–1278. 2009. View Article : Google Scholar : PubMed/NCBI
25	Buettner GR: Superoxide dismutase in redox biology: The roles of superoxide and hydrogen peroxide. Anticancer Agents Med Chem. 11:341–346. 2011. View Article : Google Scholar : PubMed/NCBI
26	Orrenius S, Gogvadze V and Zhivotovsky B: Calcium and mitochondria in the regulation of cell death. Biochem Biophys Res Commun. 460:72–81. 2015. View Article : Google Scholar : PubMed/NCBI
27	Hotchkiss RS, Strasser A, McDunn JE and Swanson PE: Cell death in disease: Mechanisms and emerging therapeutic concepts. N Engl J Med. 361:1570–1583. 2009. View Article : Google Scholar : PubMed/NCBI
28	Brenner D and Mak TW: Mitochondrial cell death effectors. Curr Opin Cell Biol. 21:871–877. 2009. View Article : Google Scholar : PubMed/NCBI
29	Zhang X, Chen Y, Gao B, Luo D, Wen Y and Ma X: Apoptotic effect of koumine on human breast cancer cells and the mechanism involved. Cell Biochem Biophys. 72:411–416. 2015. View Article : Google Scholar : PubMed/NCBI
30	Zhang WG, Chen L, Dong Q, He J, Zhao HD, Li FL and Li H: Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition in mice. Gene. 531:235–242. 2013. View Article : Google Scholar : PubMed/NCBI
31	Zhang W, Yu J, Dong Q, Zhao H, Li F and Li H: A mutually beneficial relationship between hepatocytes and cardiomyocytes mitigates doxorubicin-induced toxicity. Toxicol Lett. 227:157–163. 2014. View Article : Google Scholar : PubMed/NCBI
32	Sarada SK, Himadri P, Ruma D, Sharma SK and Pauline T: Mrinalini: Selenium protects the hypoxia induced apoptosis in neuroblastoma cells through upregulation of Bcl-2. Brain Res. 1209:29–39. 2008. View Article : Google Scholar : PubMed/NCBI
33	Rafferty TS, Beckett GJ, Walker C, Bisset YC and McKenzie RC: Selenium protects primary human keratinocytes from apoptosis induced by exposure to ultraviolet radiation. Clin Exp Dermatol. 28:294–300. 2003. View Article : Google Scholar : PubMed/NCBI
34	Burgering BM and Coffer PJ: Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature. 376:599–602. 1995. View Article : Google Scholar : PubMed/NCBI
35	Franke TF, Yang SI, Chan TO, Datta K, Kazlauskas A, Morrison DK, Kaplan DR and Tsichlis PN: The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell. 81:727–736. 1995. View Article : Google Scholar : PubMed/NCBI
36	Martindale JL and Holbrook NJ: Cellular response to oxidative stress: Signaling for suicide and survival. J Cell Physiol. 192:1–15. 2002. View Article : Google Scholar : PubMed/NCBI
37	Huang JQ, Ren FZ, Jiang YY, Xiao C and Lei XG: Selenoproteins protect against avian nutritional muscular dystrophy by metabolizing peroxides and regulating redox/apoptotic signaling. Free Radic Biol Med. 83:129–138. 2015. View Article : Google Scholar : PubMed/NCBI