P62 modulates the intrinsic signaling of UVB-induced apoptosis. Issue 3 (September 2016)

• Record Type: Journal Article
• Authors: Ito, Sachiko; Kimura, Shintaro; Warabi, Eiji; Kawachi, Yasuhiro; Yamatoji, Masanobu; Uchida, Fumihiko; Ishibashi-Kanno, Naomi; Yamagata, Kenji; Hasegawa, Shogo; Shoda, Junichi; Tabuchi, Katsuhiko; Sakai, Satoshi; Bukawa, Hiroki; Sekido, Mitsuru; Yanagawa, Toru
• Is Part Of: Journal of dermatological science. Volume 83:Issue 3(2016:Sep.)
• Page Start: 226
• Page End: 233
• Publication Date: 2016-09
• Subjects: ROS reactive oxygen species -- UV ultraviolet -- PCR polymerase chain reaction -- MEF mouse embryo fibroblast -- RIPA buffer radioimmunoprecipitation assay buffer -- PVDF polyvinylidene difluoride -- PI propidium iodide -- Bcl-2 B-cell lymphoma 2 -- Bcl-xL B-cell lymphoma-extra large -- Bax Bcl-2–associated X protein -- PUMA p53 upregulated modulator of apoptosis -- Noxa Phorbol-12-myristate-13-acetate-induced protein 1 -- ATM Ataxia telangiectasia mutated -- ATR ATM- and RAD3-related -- Stat3 signal transducer and activator of transcription 3 -- SRC SRC proto-oncogene -- PIKK phosphatidylinositol 3-kinase-related kinases -- UVRAG UV radiation resistance-associated gene protein -- Beclin1 Bcl-2 interacting protein 1; p62 -- UVB -- Apoptosis -- ROS; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2016.05.005
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: P62-deficient cells are more resistant to UVB-induced apoptosis than normal cells. Bcl-2 family expression and Stat3 phosphorylation are changed in p62-deficient cells. P62 modulates the intrinsic signaling pathway of UVB-induced apoptosis. Abstract: Background: UVB radiation is the main source of sunburn and skin cancers. Apoptosis eliminates photodamaged cells, and is thus important for preventing epidermal carcinogenesis. The cytoplasmic regulatory protein p62/A170/sequestosome 1 (p62) molecule is involved in a variety of cellular and signaling pathways. p62 is known to be and important in autophagy, but its role in UVB-induced apoptosis remains to be clarified. Objective: To investigate the role of p62 against UVB-induced apoptotic changes, using mouse embryonic fibroblasts (MEFs) derived from p62 homozygous knockout (p62 −/− ) mice. Methods: p62 −/− and wild-type (p62 +/+ ) mice and MEFs were subjected to UVB irradiation, and the resultant apoptosis was analyzed using flow cytometry, quantitative real-time PCR, and western blots. Results: Apoptosis was decreased in the p62 −/− MEFs compared to p62 +/+ MEFs in response to UVB treatment. Compared with p62 +/+ MEFs, p62 −/− MEFs expressed significantly more Bcl-2 and less Bax, and showed increased Src and Stat3 phosphorylation. Our results show that p62 regulates apoptotic pathways by modifying critical signaling intermediates such as Src and Stat3. Conclusion: p62 reduces UVB-induced apoptosis by modulating intrinsic apoptotic signaling through Src phosphorylation.