Suppression of glutamate-induced excitotoxicity by 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride in rat glial cultures.
We have screened new drugs with a view to developing effective drugs against glutamate-induced excitotoxicity. In the present work, we show effects of a new drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride against glutamate-induced excitotoxicity in primary rat glial cultures. Pretreatment of glial cells with 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride for 2 h significantly protected glial cells against glutamate-induced excitotoxicity in a time- and dose-dependent manner with an optimum concentration of 100 microM. The drug significantly reduced production of proinflammatory cytokines, tumor necrosis factor-alpha, and interlukin-1beta in glutamate-induced excitotoxicity. The drug also prevented glutamate-induced intracellular Ca2+ influx and reduced the subsequent overproduction of nitric oxide and reactive oxygen species. Furthermore, the drug preserved the mitochondrial potential and inhibited the overproduction of cytochrome c. In addition, the drug effectively attenuated the protein level changes of beta-catenin and glycogen synthase kinase-3beta. These results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride effectively protected primary cultures of rat glial cells against glutamate-induced excitotoxicity.
Kim
Eun-A
EA
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Hahn
Hoh-Gyu
HG
Kim
Key-Sun
KS
Kim
Tae Ue
TU
Choi
Soo Young
SY
Cho
Sung-Woo
SW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018836:Inflammation Mediators / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism
C550808:2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride; D016207:Cytokines; D018836:Inflammation Mediators; D009573:Nitrites; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013844:Thiazoles; D051176:beta Catenin; D018698:Glutamic Acid; D045304:Cytochromes c; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D002118:Calcium