Cytoprotective effects of proteasome beta5 subunit overexpression in lens epithelial cells

Mol Vis. 2007 Jan 16:13:31-8.

Abstract

Purpose: To determine whether the overexpression of the proteasome catalytic beta5 subunit (PSMB5) can induce the expression of the catalytic subunits beta1 and beta2, enhance proteasome activity, and exert a cytoprotective effect in lens epithelial cells.

Methods: Cells from the human lens epithelial cell line SRA01/04 (LECs) were stably transfected either with a plasmid expressing the proteasome catalytic subunit beta5 or with an empty plasmid. beta-5-expressing LECs and controls were analyzed for the expression of beta1, beta2, beta5, and alpha6 proteasome subunits; chymotrypsin-like (CT-L) and peptidylglutamyl-peptide hydrolase (PGPH) catalytic activities; as well as for the accumulation of carbonylated proteins, rates of cell viability, and apoptosis after oxidative stress.

Results: Stable expression of the beta5 proteasome subunit resulted in increased expression of the catalytic subunits beta1 and beta2, increased CT-L and PGPH proteasome activities, and increased resistance to accumulation of carbonylated proteins and cell death after oxidative stress.

Conclusions: The proteasome activity can be genetically "upregulated" in lens cells by overexpression of the beta5 catalytic subunit. The resulting increase in proteasome activity leads to a decrease in the accumulation of oxidized proteins and enhanced cell survival following oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival
  • Chymotrypsin / metabolism
  • Cytoprotection / physiology*
  • Endopeptidases / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Eye Proteins / metabolism
  • Humans
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / physiology
  • Oxidation-Reduction
  • Oxidative Stress / physiology
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Carbonylation / physiology

Substances

  • Eye Proteins
  • Endopeptidases
  • Chymotrypsin
  • PSMB5 protein, human
  • Proteasome Endopeptidase Complex
  • peptidylglutamylpeptide hydrolase