title: Fascin2 regulates cisplatin-induced apoptosis in NRK-52E cells.
abstract: Previous studies have shown that the aging kidney has a marked loss of α(E)-catenin in proximal tubular epithelium. α-Catenin, a key regulator of the actin cytoskeleton, interacts with a variety of actin-binding proteins. Cisplatin-induced loss of fascin2, an actin bundling protein, was observed in cells with a stable knockdown of α(E)-catenin (C2 cells), as well as in aging (24 mon), but not young (4 mon), kidney. Fascin2 co-localized with α-catenin and the actin cytoskeleton in NRK-52E cells. Knockdown of fascin2 increased the susceptibility of tubular epithelial cells to cisplatin-induced injury. Overexpression of fascin2 in C2 cells restored actin stress fibers and attenuated the increased sensitivity of C2 cells to cisplatin-induced apoptosis. Interestingly, fascin2 overexpression attenuated cisplatin-induced mitochondrial dysfunction and oxidative stress in C2 cells. These data demonstrate that fascin2, a putative target of α(E)-catenin, may play important role in preventing cisplatin-induced acute kidney injury.
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: LaNita
authors.initials: L
authors.lastname: Nichols
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grunz-Borgmann
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States; Dalton Cardiovascular Research Center, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States; Dalton Cardiovascular Research Center, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Meininger
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Domeier
authors.affiliation: Dalton Cardiovascular Research Center, School of Medicine, University of Missouri, Columbia, MO 65212, United States; Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO 65212, United States.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Baines
authors.affiliation: Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, MO 65212, United States. Electronic address: parrishar@health.missouri.edu.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Parrish
mesh_terms: D000375:Aging; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002945:Cisplatin / Q000633:toxicity*; D005786:Gene Expression Regulation; D007668:Kidney / Q000166:cytology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D051177:Catenins; D008840:Microfilament Proteins; C020324:fascin; D002945:Cisplatin
keywords: Actin; Aging; Apoptosis; Fascin2; Mitochondria; α-Catenin