Fascin2 regulates cisplatin-induced apoptosis in NRK-52E cells

Toxicol Lett. 2017 Jan 15;266:56-64. doi: 10.1016/j.toxlet.2016.11.021. Epub 2016 Dec 15.

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.

Keywords: Actin; Aging; Apoptosis; Fascin2; Mitochondria; α-Catenin.

MeSH terms

  • Aging
  • Animals
  • Antineoplastic Agents / toxicity*
  • Apoptosis / drug effects*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Catenins / genetics
  • Catenins / metabolism
  • Cell Line
  • Cisplatin / toxicity*
  • Gene Expression Regulation
  • Kidney / cytology
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Protein Transport
  • Rats

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • Catenins
  • Microfilament Proteins
  • fascin
  • Cisplatin