PMID- 35091949 OWN - NLM STAT- MEDLINE DCOM- 20220530 LR - 20220530 IS - 1614-7499 (Electronic) IS - 0944-1344 (Linking) VI - 29 IP - 27 DP - 2022 Jun TI - Cadmium induces apoptosis and autophagy in swine small intestine by downregulating the PI3K/Akt pathway. PG - 41207-41218 LID - 10.1007/s11356-022-18863-2 [doi] AB - Cadmium (Cd) is an environmental contaminant, which is potentially toxic. It is well known that Cd can accumulate in the liver and kidney and cause serious damage. However, few studies have investigated the mechanism of intestinal damage induced by Cd in swine. Here, we established Cd poisoning models in vivo and in vitro to explore the mechanism of intestinal injury induced by Cd in swine. The morphology of intestinal tissue cells was observed by TUNEL staining and electron microscopy, and the morphology of IPEC-J2 cells was observed by flow cytometry, Hoechst staining, and MDC staining. Cell morphological observations revealed that Cd treatment induced ileal apoptosis and autophagy. The effects of Cd on the PI3K/Akt pathway, as well as on apoptosis and autophagy-related protein expression in intestinal cells, were analyzed by western blot (WB) and the expression of mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that Cd induced autophagy by increasing the levels of autophagy markers Beclin1, Autophagy-associated gene 5 (ATG5), Autophagy-associated gene 16 (ATG16), and Microtubule-associated protein light chains 3-2 (LC3-II), and by reducing the expression levels of Mechanistic target of rapamycin kinase (mTOR) and Microtubule-associated protein light chains 3-1 (LC3-I). Cell apoptosis was induced by increasing the expression of apoptosis markers Bcl-2 associated X protein (Bax), Cysteinyl aspartate specific proteinase 9 (Caspase9), cleaved Caspase9, Cysteinyl aspartate specific proteinase 3 (Caspase3), and cleaved Caspase3, and by reducing the expression of B cell lymphoma/leukemia 2 (Bcl-2). At the same time, Cd decreased the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and their phosphorylation. We treated IPEC-J2 cells with the PI3K activator 740Y-P and analyzed the morphological changes as well as autophagy and apoptosis-related gene expression. The results showed that 740Y-P could reduce apoptosis and autophagy induced by Cd. In conclusion, our findings suggest that Cd induces intestinal apoptosis and autophagy in swine by inactivating the PI3K/Akt signaling pathway. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Zhang, Haoran AU - Zhang H AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. FAU - Huang, Jiaqiang AU - Huang J AD - Department of Nutrition and Health, College of Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100083, People's Republic of China. FAU - Yang, Jie AU - Yang J AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. FAU - Cai, Jingzeng AU - Cai J AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. FAU - Liu, Qi AU - Liu Q AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. FAU - Zhang, Xintong AU - Zhang X AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. FAU - Bao, Jun AU - Bao J AD - College of Animal Science, Northeast Agricultural University, Harbin, 150030, People's Republic of China. FAU - Zhang, Ziwei AU - Zhang Z AUID- ORCID: 0000-0002-5705-4611 AD - College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, People's Republic of China. zhangziwei@neau.edu.cn. AD - Key Laboratory of the Provincial Education, Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Harbin, 150030, People's Republic of China. zhangziwei@neau.edu.cn. LA - eng GR - YQ2021C021/Heilongjiang Provincial Natural Science Foundation for Outstanding Youth/ GR - No. CARS 35-04/Earmarked Fund for China Agriculture Research System/ GR - LBH-Q18018/Heilongjiang Provincial Postdoctoral Science Foundation/ GR - 2020TD22/Central Public-interest Scientific Institution Basal Research Fund, Chinese Academy of Fishery Sciences/ PT - Journal Article DEP - 20220128 PL - Germany TA - Environ Sci Pollut Res Int JT - Environmental science and pollution research international JID - 9441769 RN - 0 (Microtubule-Associated Proteins) RN - 00BH33GNGH (Cadmium) RN - 30KYC7MIAI (Aspartic Acid) RN - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis MH - Aspartic Acid MH - Autophagy MH - Cadmium/toxicity MH - Intestine, Small MH - Microtubule-Associated Proteins/metabolism MH - Phosphatidylinositol 3-Kinase/pharmacology MH - *Phosphatidylinositol 3-Kinases/metabolism MH - *Proto-Oncogene Proteins c-akt/metabolism MH - Swine MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - Apoptosis OT - Autophagy OT - Cadmium exposure OT - Environmental pollution OT - PI3K/Akt pathway OT - Swine small intestine EDAT- 2022/01/30 06:00 MHDA- 2022/05/31 06:00 CRDT- 2022/01/29 05:47 PHST- 2021/09/29 00:00 [received] PHST- 2022/01/21 00:00 [accepted] PHST- 2022/01/30 06:00 [pubmed] PHST- 2022/05/31 06:00 [medline] PHST- 2022/01/29 05:47 [entrez] AID - 10.1007/s11356-022-18863-2 [pii] AID - 10.1007/s11356-022-18863-2 [doi] PST - ppublish SO - Environ Sci Pollut Res Int. 2022 Jun;29(27):41207-41218. doi: 10.1007/s11356-022-18863-2. Epub 2022 Jan 28.