Expression of cystatin C prevents oxidative stress-induced death in PC12 cells.
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.
Nishiyama
Keiji
K
Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Japan.
Konishi
Akio
A
Nishio
Chika
C
Araki-Yoshida
Kiyomi
K
Hatanaka
Hiroshi
H
Kojima
Masami
M
Ohmiya
Yoshihiro
Y
Yamada
Masashi
M
Koshimizu
Hisatsugu
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004351:Drug Resistance / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000009:adverse effects; D016716:PC12 Cells; D051381:Rats
C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D003546:Cysteine Endopeptidases; D010100:Oxygen