Arsenite exposure-induced premature senescence followed by SASP induction in Huh7 cells is maintained even after cessation of arsenite exposure
-
- OKAMURA Kazuyuki
- Health and Environmental Risk Division, National Institute for Environmental Studies
-
- SUZUKI Takehiro
- Health and Environmental Risk Division, National Institute for Environmental Studies
-
- NOHARA Keiko
- Health and Environmental Risk Division, National Institute for Environmental Studies
Bibliographic Information
- Other Title
-
- 無機ヒ素曝露により誘導された肝細胞の細胞老化およびSASP因子の増加は曝露を中止後も維持される
Abstract
<p>Arsenite-induced cancer is known to be development after a latent period, even after the exposure is discontinued. Previously, we have shown that arsenite exposure induces premature senescence and senescence-associated secretory phenotype (SASP) factors in hepatocytes. However, it is unclear whether arsenite exposure-induced premature senescence and SASP factors are maintained even after cessation of arsenite exposure. In this study, we examined whether the arsenite exposure-induced premature senescence and SASP factors in hepatocytes persist after cessation of arsenite exposure.</p><p>As a result, senescent features such as morphological changes (enlarged and flatten) and changes of mRNA levels of senescence markers (P21 induction and LAMINB1 reduction) were maintained after 100 hours from cessation of 5 μM sodium arsenite exposure for 72 hours in Huh-7 cells. At that time, mRNA levels of SASP factors (MMP1, MMP3, MMP10, GDF15, PAI-1 and IL-6) were also significantly increased. We further confirmed that senescent cells still exist 7 days after cessation of the exposure by performing SA-β-gal staining. Furthermore, almost SASP factors that were upregulated by arsenite exposure in hepatocytes showed a positive correlation between increased expression and poor prognosis in human hepatocellular carcinoma by analyzing TCGA database.</p><p>These results showed that arsenite exposure-induced premature senescence followed by SASP induction is maintained in hepatocytes even after cessation of arsenite exposure and the SASP factors can be involved in progression of cancer.</p>
Journal
-
- Annual Meeting of the Japanese Society of Toxicology
-
Annual Meeting of the Japanese Society of Toxicology 50.1 (0), O2-01-, 2023
The Japanese Society of Toxicology
- Tweet
Details 詳細情報について
-
- CRID
- 1390580870561199232
-
- Text Lang
- ja
-
- Data Source
-
- JaLC
-
- Abstract License Flag
- Disallowed