Expression of cystatin C prevents oxidative stress-induced death in PC12 cells

Brain Res Bull. 2005 Sep 30;67(1-2):94-9. doi: 10.1016/j.brainresbull.2005.05.020.


Cystatin C, an inhibitor of cysteine proteinases, is suggested to be involved in oxidative stress-induced apoptosis of cultured CNS neurons and various neuronal diseases in vivo; however, little is known about its mechanism of action. To address the role cystatin C plays in oxidative stress-induced neuronal cell death, we established PC12 cell lines that stably expressed rat cystatin C. These cystatin C-expressing PC12 cells showed remarkable resistance to high (50%) oxygen atmosphere. This resistance correlate with expression levels of cystatin C, demonstrating that cystatin C has a protective effect on high oxygen-induced cell death. In contrast, in a normal (20%) oxygen atmosphere neither control nor cystatin C-expressing PC12 cells showed a significant change in the number of living cells, indicating that cystatin C does not play an important role in the regulation of cellular proliferation. Furthermore, the cystatin C-expressing cell line also resisted other oxidative stresses, including glutamate- and 13-L-hydroperoxylinoleic acid (LOOH)-induced cell death. These results demonstrate that cystatin C has protective effects against various oxidative stresses that induce cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Brain / metabolism
  • Brain / physiopathology
  • Cystatin C
  • Cystatins / genetics
  • Cystatins / metabolism*
  • Cystatins / pharmacology
  • Cysteine Endopeptidases / metabolism
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Drug Resistance / physiology
  • Glutamic Acid / pharmacology
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuroprotective Agents / metabolism*
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Oxygen / adverse effects
  • PC12 Cells
  • Rats


  • Cst3 protein, rat
  • Cystatin C
  • Cystatins
  • Neuroprotective Agents
  • Glutamic Acid
  • Cysteine Endopeptidases
  • Oxygen