title: The reversal of paraquat-induced mitochondria-mediated apoptosis by cycloartenyl ferulate, the important role of Nrf2 pathway.
abstract: In this study, we demonstrate the protective effects of Cycloartenyl ferulate (CF) against Paraquat (PQ)-induced cytotoxicity and elucidate the underlying molecular mechanisms. The results show that, CF could reverse the PQ-induced growth inhibition and release of lactate dehydrogenase in HK-2 human proximal tubular cells. Treatment with PQ induced apoptosis in HK-2 cells, as evidenced by accumulation of sub-G1 cell population, chromatin condensation, DNA fragmentation, and translocation of phosphatidylserine, which were significantly attenuated by co-incubation with CF. Mitochondria-mediated apoptosis pathway contributed importantly to PQ-induced apoptosis, as revealed by the activation of caspase-3/-9, cleavage of PARP, depletion of mitochondrial membrane potential regulated by Bcl-2 family members, and overproduction of reactive oxygen species, which were also effectively blocked by CF. Moreover, treatments of PQ strongly inhibited the expression of Nrf2 and the downstream effectors, HO1 and NQO1. However, co-treatment with CF effectively reversed this action of PQ. Furthermore, silencing of Nrf2 by the siRNA technique significantly blocked the cytoprotective effects of CF against PQ-induced apoptosis, which suggest the important role of Nrf2 signaling pathway an cell apoptosis induced by PQ. Taken together, this study provides a novel strategy for molecular intervention against PQ-induced nephrotoxicity by using phytochemicals.
authors: Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, 2# Fuxue Lane, Lucheng District, Wenzhou 325000, Zhejiang, China. Electronic address: honggl98@126.com.
authors: Guang-Liang
authors: GL
authors: Hong
authors: Jia-Ming
authors: JM
authors: Liu
authors: Guang-Ju
authors: GJ
authors: Zhao
authors: Lei
authors: L
authors: Wang
authors: Guang
authors: G
authors: Liang
authors: Bin
authors: B
authors: Wu
authors: Meng-Fang
authors: MF
authors: Li
authors: Qiao-Meng
authors: QM
authors: Qiu
authors: Zhong-Qiu
authors: ZQ
authors: Lu
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010269:Paraquat / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000700:Analgesics; D003373:Coumaric Acids; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; C540967:cycloartenyl ferulate; D010269:Paraquat
keywords: Apoptosis; Cycloartenyl ferulate; Nephrotoxicity; Nrf2 pathway; Paraquat