title: Necrostatin-1 attenuates ischemia injury induced cell death in rat tubular cell line NRK-52E through decreased Drp1 expression.
abstract: Necrostatin-1 (Nec-1) inhibits necroptosis and is usually regarded as having no effect on other cell deaths. Here, this study explored whether the addition of Nec-1 has an effect on cell death induced by simulated ischemia injury in rat tubular cell line NRK-52E. In addition, we also investigated the mechanism of Nec-1 attenuates cell death in this renal ischemia model. The NRK-52E cells were incubated with TNF-α + antimycinA (TA) for 24 h with or without Nec-1. Cell death was observed under fluorescent microscope and quantified by flow cytometry. Cell viabilities were detected by MTT assay. The protein expression of dynamin-related protein 1 (Drp1) was detected by Western blotting and immunofluorescence assay. Increased cell death in simulated ischemia injury of NRK-52E cells were markedly attenuated in the Nec-1 pretreated ischemia injury group. Meanwhile, cell viability was significantly improved after using Nec-1. In addition, we also observed that the protein expression of Drp1, a mediator of mitochondrial fission, was significantly increased in simulated ischemia injury group. Increased Drp1 expression in the ischemia injury group can be abolished by Nec-1 or Drp1-knock down, accompanied with decreased cell death and improved cell viabilities. These results suggest that Nec-1 may inhibit cell death induced by simulated ischemia injury in the rat tubular cell line NRK-52E through decreased Drp1 expression.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Fen
authors.initials: F
authors.lastname: Jiang
authors.forename: Yuanhan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jialun
authors.initials: J
authors.lastname: Luo
authors.forename: Shuangxin
authors.initials: S
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ye
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wang
authors.affiliation: Southern Medical University, Guangzhou 510080, China. xllianggd@163.com.
authors.forename: Xinling
authors.initials: X
authors.lastname: Liang
authors.affiliation: Southern Medical University, Guangzhou 510080, China. shiwei.gd@139.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C507699:necrostatin-1; D000968:Antimycin A; D000255:Adenosine Triphosphate; C519851:Dnm1l protein, rat; D034281:Dynamins