IRE1 and CaMKKβ pathways to reveal the mechanism involved in microcystin-LR-induced autophagy in mouse ovarian cells.

payth.elady61 shared this article with you from Inoreader IRE1 and CaMKKβ pathways to reveal the mechanism involved in microcystin-LR-induced autophagy in mouse ovarian cells. Via pubmed: autophagy IRE1 and CaMKKβ pathways to reveal the mechanism involved in microcystin-LR-induced autophagy in mouse ovarian cells. Food Chem Toxicol. 2020 Dec 05;:111911 Authors: Ma Y, Liu H, Du X, Petlulu P, Chen X, Wang R, Zhang S, Tian Z, Shi L, Guo H, Zhang H Abstract Microcystin-LR (MC-LR) is an emerging water pollutant produced by eutrophication of water. It could be absorbed into human body via contaminated food and drinking water causing severe reproductive toxicity. Previous studies showed that MC-LR could regulate autophagy by inducing endoplasmic reticulum (ER) stress thereby causing female reproductive toxicity. However, the molecular mechanisms of MC-LR-induced autophagy remain to be elucidated. It is known that IRE1 and CaMKKβ pathways are two important pathways involved in autophagy induced by ER stress. Hence, this paper investigated the roles of both pathways in MC-LR-induced autophagy in mouse ovarian cells. The results showed that MC-LR significantly up-regulated the expression of autophagy marker proteins LC3Ⅱ and BECLIN1 and down-regulated the expression of P62 in vivo and in vitro. MC-LR-caused increase of autophagosomes could be observed in KK-1 cells by MDC staining. MC-LR induced the formation of autolysosomes as in dicated by the overlap of LAMP1 and LC3. Meanwhile, MC-LR significantly activated the proteins in IRE1 pathway (IRE1, XBP1 and JNK) and in CaMKKβ pathway (CaMKKβ, AMPK, mTOR). Furthermore, MC-LR caused weight loss and ovarian histopathological damage in mice. In contrast, after the expression and function of IRE1 and CaMKKβ with siRNA in vitro and by inhibitors (4μ8C and STO-609, respectively) in vivo, the up-regulation of LC3Ⅱ and BECLIN1 and the degradation of P62 induced by MC-LR were significantly suppressed. MC-LR-induced autophagosomes in KK-1 cells and autolysosomes in mouse ovarian cells were also decreased. Moreover, the knockdown of IRE1 and CaMKKβ relieved MC-LR-induced histopathological injury to mouse ovaries. These results indicated that MC-LR induced ovarian cell autophagy and ovarian injury via IRE1 and CaMKKβ pathways. This study is the first study revealing the molecular mechanisms of MC-LR-induced autophagy of ovarian cells and providing new insights into the female reproductive toxicity of MC-LR. PMID: 33290805 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.