p120 catenin attenuates the angiotensin II-induced apoptosis of human umbilical vein endothelial cells by suppressing the mitochondrial pathway

Zhang,Yan; Zou,Chenshuang; Yang,Shuwen; Fu,Jing

doi:10.3892/ijmm.2016.2476

p120 catenin attenuates the angiotensin II-induced apoptosis of human umbilical vein endothelial cells by suppressing the mitochondrial pathway

Authors:
- Yan Zhang
- Chenshuang Zou
- Shuwen Yang
- Jing Fu
View Affiliations

Affiliations: Department of VIP Medical Service, Beijing Hospital, Beijing 100730, P.R. China, Editorial Department of Chinese Journal of Neuroimmunology and Neurology, Beijing Hospital, Beijing 100730, P.R. China
Published online on: February 1, 2016 https://doi.org/10.3892/ijmm.2016.2476
Pages: 623-630
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Hypertension impairs the morphological and functional integrity of circulation. Previous research has shown that the loss of endothelial cells (ECs) is a common event in many cardiovascular diseases. p120 catenin (p120ctn) plays an important role in the regulation of inflammatory responses in ECs. However, the functional significance of p120ctn in angiotensin II (AngII)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) had not previously received much scholarly attention. In the present study, using western blot analysis and RT-PCR, we found that AngII-induced cell apoptosis was correlated with a significant decrease in p120ctn expression. The effect of AngII on cell viability was measured by CCK-8 assay. Knockdown of p120ctn with small hairpin RNA (shRNA) increased AngII-induced apoptosis of HUVECs, as demonstrated by Annexin V/PI staining and flow cytometric analysis. Knockdown of p120ctn with shRNA also increased cytochrome c release into the cytoplasm, and cleaved caspase-3 and -9 protein expression. These were accompanied by a decrease in the Bcl-2/Bax ratio (Bcl-2 and Bax protein expression were measured by western blot analysis), and in mitochondrial membrane potential, as measured using JC-1. Overexpression of p120ctn with adenovirus produced opposite effects. In the present study, we demonstrated that p120ctn attenuated AngII‑induced apoptosis of HUVECs through the mitochondria-dependent pathway, suggesting that p120ctn plays a critical role in protecting ECs against apoptosis during hypertension.

View Figures

View References

1	Lee R, Channon KM and Antoniades C: Therapeutic strategies targeting endothelial function in humans: clinical implications. Curr Vasc Pharmacol. 10:77–93. 2012. View Article : Google Scholar
2	Shi H, Sheng B, Zhang F, Wu C, Zhang R, Zhu J, Xu K, Kuang Y, Jameson SC, Lin Z, et al: Kruppel-like factor 2 protects against ischemic stroke by regulating endothelial blood brain barrier function. Am J Physiol Heart Circ Physiol. 304:H796–H805. 2013. View Article : Google Scholar : PubMed/NCBI
3	Wada K, Gerbaudo VH and Spector M: Effects of PDGF-BB and OP-1 on mesenchymal stem cells in a porous mineral block. Int J Periodontics Restorative Dent. 33:e72–e78. 2013. View Article : Google Scholar : PubMed/NCBI
4	Xie F, Cai W, Liu Y, Li Y, Du B, Feng L and Qiu L: Vaccarin attenuates the human EA.hy926 endothelial cell oxidative stress injury through inhibition of Notch signaling. Int J Mol Med. 35:135–142. 2015.
5	Wang C, He Y, Yang M, Sun H, Zhang S and Wang C: Safflor yellow B suppresses angiotensin II-mediated human umbilical vein cell injury via regulation of Bcl-2/p22(phox) expression. Toxicol Appl Pharmacol. 273:59–67. 2013. View Article : Google Scholar : PubMed/NCBI
6	Dimmeler S, Rippmann V, Weiland U, Haendeler J and Zeiher AM: Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. Circ Res. 81:970–976. 1997. View Article : Google Scholar : PubMed/NCBI
7	Mendell JT and Olson EN: MicroRNAs in stress signaling and human disease. Cell. 148:1172–1187. 2012. View Article : Google Scholar : PubMed/NCBI
8	Caporali A and Emanueli C: MicroRNA regulation in angiogenesis. Vascul Pharmacol. 55:79–86. 2011. View Article : Google Scholar : PubMed/NCBI
9	Wang J, Sun P, Bao Y, Dou B, Song D and Li Y: Vitamin E renders protection to PC12 cells against oxidative damage and apoptosis induced by single-walled carbon nanotubes. Toxicol In Vitro. 26:32–41. 2012. View Article : Google Scholar
10	Paravicini TM and Touyz RM: Redox signaling in hypertension. Cardiovasc Res. 71:247–258. 2006. View Article : Google Scholar : PubMed/NCBI
11	Sata M and Fukuda D: Crucial role of renin-angiotensin system in the pathogenesis of atherosclerosis. J Med Invest. 57:12–25. 2010. View Article : Google Scholar : PubMed/NCBI
12	Reynolds AB, Roesel DJ, Kanner SB and Parsons JT: Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol. 9:629–638. 1989. View Article : Google Scholar : PubMed/NCBI
13	Wang M, Li N, Li J, Ma Y, Li D, Qin L, Wang X and Wu R: Involvement of p120 in LPS-induced NF-kappaB activation and IL-8 production in human bronchial epithelial cells. Toxicol Lett. 195:75–81. 2010. View Article : Google Scholar : PubMed/NCBI
14	Reynolds AB, Daniel J, McCrea PD, Wheelock MJ, Wu J and Zhang Z: Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Mol Cell Biol. 14:8333–8342. 1994. View Article : Google Scholar : PubMed/NCBI
15	Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Miyazawa K, Kitamura N, Johnson KR, Wheelock MJ, Matsuyoshi N, Takeichi M and Fumiaki Ito: Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes. J Cell Biol. 128:949–957. 1995. View Article : Google Scholar : PubMed/NCBI
16	Piedra J, Miravet S, Castaño J, Pálmer HG, Heisterkamp N, García de Herreros A and Duñach M: p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction. Mol Cell Biol. 23:2287–2297. 2003. View Article : Google Scholar : PubMed/NCBI
17	Kim SW, Park JI, Spring CM, Sater AK, Ji H, Otchere AA, Daniel JM and McCrea PD: Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. Nat Cell Biol. 6:1212–1220. 2004. View Article : Google Scholar : PubMed/NCBI
18	Prokhortchouk A, Hendrich B, Jørgensen H, Ruzov A, Wilm M, Georgiev G, Bird A and Prokhortchouk E: The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev. 15:1613–1618. 2001. View Article : Google Scholar : PubMed/NCBI
19	Anastasiadis PZ, Moon SY, Thoreson MA, Mariner DJ, Crawford HC, Zheng Y and Reynolds AB: Inhibition of RhoA by p120 catenin. Nat Cell Biol. 2:637–644. 2000. View Article : Google Scholar : PubMed/NCBI
20	Hong JY, Park JI, Cho K, Gu D, Ji H, Artandi SE and McCrea PD: Shared molecular mechanisms regulate multiple catenin proteins: canonical Wnt signals and components modulate p120-catenin isoform-1 and additional p120 subfamily members. J Cell Sci. 123:4351–4365. 2010. View Article : Google Scholar : PubMed/NCBI
21	Reynolds AB: p120-catenin: past and present. Biochim Biophys Acta. 1773:2–7. 2007. View Article : Google Scholar
22	Reynolds AB and Roczniak-Ferguson A: Emerging roles for p120-catenin in cell adhesion and cancer. Oncogene. 23:7947–7956. 2004. View Article : Google Scholar : PubMed/NCBI
23	Wang YL, Malik AB, Sun Y, Hu S, Reynolds AB, Minshall RD and Hu G: Innate immune function of the adherens junction protein p120-catenin in endothelial response to endotoxin. J Immunol. 186:3180–3187. 2011. View Article : Google Scholar : PubMed/NCBI
24	O'Donnell JJ III, Zhuge Y, Holian O, Cheng F, Thomas LL, Forsyth CB and Lum H: Loss of p120 catenin upregulates transcription of pro-inflammatory adhesion molecules in human endothelial cells. Microvasc Res. 82:105–112. 2011. View Article : Google Scholar : PubMed/NCBI
25	Perez-Moreno M, Davis MA, Wong E, Pasolli HA, Reynolds AB and Fuchs E: p120-catenin mediates inflammatory responses in the skin. Cell. 124:631–644. 2006. View Article : Google Scholar : PubMed/NCBI
26	Liu J, Zhang FF, Li L, Yang J, Liu J, Guan YY and Du YH: ClC-3 deficiency prevents apoptosis induced by angiotensin II in endothelial progenitor cells via inhibition of NADPH oxidase. Apoptosis. 18:1262–1273. 2013. View Article : Google Scholar : PubMed/NCBI
27	Ott M, Gogvadze V, Orrenius S and Zhivotovsky B: Mitochondria, oxidative stress and cell death. Apoptosis. 12:913–922. 2007. View Article : Google Scholar : PubMed/NCBI
28	Mignotte B and Vayssiere JL: Mitochondria and apoptosis. Eur J Biochem. 252:1–15. 1998. View Article : Google Scholar : PubMed/NCBI
29	Perez-Moreno M, Song W, Pasolli HA, Williams SE and Fuchs E: Loss of p120 catenin and links to mitotic alterations, inflammation, and skin cancer. Proc Natl Acad Sci USA. 105:15399–15404. 2008. View Article : Google Scholar : PubMed/NCBI
30	Liu N, Li AL, Zhou XP, Chen Q and Cao W: P120 catenin attenuates lipopolysaccharide-induced blood-brain barrier dysfunction and inflammatory responses in human brain micro-vascular endothelial cells. Int J Clin Exp Pathol. 8:4204–4212. 2015.
31	Qin L, Qin S, Zhang Y, Zhang C, Ma H, Li N, Liu L, Wang X and Wu R: p120 modulates LPS-induced NF-κB activation partially through RhoA in bronchial epithelial cells. Biomed Res Int. 2014:9323402014. View Article : Google Scholar
32	Ye QF, Zhang YC, Peng XQ, Long Z, Ming YZ and He LY: Silencing Notch-1 induces apoptosis and increases the chemo-sensitivity of prostate cancer cells to docetaxel through Bcl-2 and Bax. Oncol Lett. 3:879–884. 2012.PubMed/NCBI
33	Teichert-Kuliszewska K, Tsoporis JN, Desjardins JF, Yin J, Wang L, Kuebler WM and Parker TG: Absence of the calcium-binding protein, S100A1, confers pulmonary hypertension in mice associated with endothelial dysfunction and apoptosis. Cardiovasc Res. 105:8–19. 2015. View Article : Google Scholar
34	Efrati S, Berman S, Goldfinger N, Erez N, Averbukh Z, Golik A, Rotter V and Weissgarten J: Enhanced angiotensin II production by renal mesangium is responsible for apoptosis/proliferation of endothelial and epithelial cells in a model of malignant hypertension. J Hypertens. 25:1041–1052. 2007. View Article : Google Scholar : PubMed/NCBI
35	Rojas E, Rodríguez-Molina D, Bolli P, Israili ZH, Faría J, Fidilio E, Bermúdez V and Velasco M: The role of adiponectin in endothelial dysfunction and hypertension. Curr Hypertens Rep. 16:4632014. View Article : Google Scholar : PubMed/NCBI
36	Misiti F, Orsini F, Clementi ME, Lattanzi W, Giardina B and Michetti F: Mitochondrial oxygen consumption inhibition importance for TMT-dependent cell death in undifferentiated PC12 cells. Neurochem Int. 52:1092–1099. 2008. View Article : Google Scholar : PubMed/NCBI
37	Reagan-Shaw S, Nihal M, Ahsan H, Mukhtar H and Ahmad N: Combination of vitamin E and selenium causes an induction of apoptosis of human prostate cancer cells by enhancing Bax/Bcl-2 ratio. Prostate. 68:1624–1634. 2008. View Article : Google Scholar : PubMed/NCBI