Identification and functional analysis of senescence-associated secretory phenotype of premature senescent hepatocytes induced by hexavalent chromium

• Published in: Ecotoxicology and environmental safety 2021-03, Vol.211, p.111908, Article 111908
• Main Authors: Ma, Yu, Liang, Yuehui, Liang, Ningjuan, Zhang, Yujing, Xiao, Fang
• Format: Article
• Language: English
• Subjects: Alpha-enolase (ENO1); Cell Line; Cellular Senescence; Chromatography, Liquid; Chromium - toxicity; Hepatocytes - metabolism; Hexavalent chromium [Cr(VI)]; Humans; Microfilament Proteins - metabolism; Peroxiredoxin 2 (PRDX2); Phenotype; Premature senescence; Senescence-associated secretion phenotype (SASP); Signal Transduction; Tandem Mass Spectrometry; Up-Regulation
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2021.111908

Hexavalent chromium [Cr(VI)] is a common heavy metal pollutant that can cause a number of human disease, including inflammation and cancer. Senescent cells can secrete a variety of molecules known as senescence-associated secretory phenotype (SASP). Our previous studies have confirmed that Cr(VI) can induce premature senescence in L02 hepatocytes, but the composition and the function of the related SASP are still unknown. In order to understand the components of SASP secreted by senescent L02 hepatocytes under the action of Cr(VI), we applied LC-MS/MS-based label-free protein quantification. We found that three SASP components including Coactosin-like protein 1 (COTL1), Alpha-enolase (ENO1), and Peroxiredoxin 2 (PRDX2) were up-regulated, which were confirmed by western blotting and qRT-PCR. Evidence suggested that SASP may promote the development of tumor through chronic inflammatory response, therefore we identified and analyzed the potential biological functions and signaling pathways of these three SASP components using GO and KEGG methods. The interaction between SASP components was analyzed by STRING, and verified by Co-IP. We also found that ENO1 and PRDX2, which have direct interaction, can inhibit the growth and proliferation of wildtype hepatocytes and premature senescent hepatocytes, but can promote the proliferation and behavioral changes of liver tumor cells. The present study provides valuable clues for elucidation of the carcinogenic mechanism of Cr(VI), especially for further prevention and targeted treatment of Cr(VI)-related cancer. •Cr(VI) induces premature senescence in L02 hepatocytes.•Cr(VI)-induced SASP components include COTL1, ENO1, PRDX2.•ENO1 directly interacts with PRDX2 in Cr(VI)-induced senescent hepatocytes.•ENO1 and PRDX2 regulate proliferation of wildtype/senescent hepatocytes and HCCLM3.