Mimosine prevents the death of glucose-deprived immunostimulated astrocytes by scavenging peroxynitrite.
Immunostimulated astrocytes become highly vulnerable to glucose deprivation (Choi and Kim: J Neurosci Res 54:870-875, 1998a). The increased vulnerability is caused by the enhanced level of peroxynitrite endogenously produced in glucose-deprived immunostimulated astrocytes. In the present study, we report that the plant amino acid mimosine can attenuate the increased death by scavenging peroxynitrite. Treatment with mimosine blocked the increase of nitrotyrosine immunoreactivity, a marker of peroxynitrite, in glucose-deprived immunostimulated astrocytes. Furthermore, mimosine directly inhibited the nitration of tyrosine residues of bovine serum albumin and the oxidation of dihydrorhodamine-123 to rhodamine-123 by peroxynitrite. Mimosine has been used experimentally as a cell cycle G1/S phase transition blocker (Lalande: Exp Cell Res 186:332-339, 1990; Hoffman et al.: Cytometry 12:26-32, 1991). Flow cytometry analysis, however, showed that the cytoprotective effect of mimosine was not attributed to its inhibition of cell cycle progression. Furthermore, under our experimental conditions, mimosine did not alter the levels of cell cycle regulatory proteins, including p21(WAF1/CIP1), cyclins D1 and E, and proliferating cell nuclear antigen. In addition, cyclin-dependent kinase inhibitors olomoucine and roscovitine did not block the increased death. These results indicate that mimosine inhibits the augmented death of glucose-deprived immunostimulated astrocytes by scavenging peroxynitrite rather than suppressing the cell cycle progression.
Department of Pharmacology, College of Medicine, Laboratory of Neurodegenerative Diseases, Ewha Institute of Neuroscience, Ewha Women's University, Seoul, Republic of Korea.
Jung-Jin
JJ
Choi
Yu-Kyoung
YK
Oh
Hyun-Soo
HS
Kim
Hyoung-Chun
HC
Kim
Kwang Ho
KH
Ko
Won-Ki
WK
Kim
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005947:Glucose / Q000276:immunology / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008898:Mimosine / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000276:Adjuvants, Immunologic; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D030421:Peroxynitrous Acid; D008898:Mimosine; D007371:Interferon-gamma; D005947:Glucose