상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

COX-2 regulates the insulin-like growth factor 1-induced potentiation of Zn2+-toxicity in primary cortical culture

Authors 

J Y ImD Y KimK W LeeJ B KimJ K LeeDong Sik KimYoung Ik LeeK S HaC O JoeP L Han

Publisher 

American Society for Pharmacology and Experimental Therapeutics (ASPET)

Issue Date 

2004

Citation 

Molecular Pharmacology, vol. 66, no. 3, pp. 368-376

Abstract 

The pretreatment of cultured cortical neurons with neurotrophic factors markedly potentiates the cytotoxicity induced by low concentrations of Zn2+ or excitotoxins. In the current study, we investigated the mechanism underlying the insulin-like growth factor- I (IGF-I)-induced Zn2+ toxicity potentiation. The pretreatment of primary cortical cultures for more than 12 h with 100 ng/ml of IGF-I increased the cytotoxicity induced by 80 μM Zn2+ by more than 2-fold. The IGF-I.enhanced cell death was blocked by the COX-2.specific inhibitors N-[2-(cyclohexyloxyl)-4-nitrophenyl]- methane sulfonamide (NS-398; 10.100 μM) and 1-[(4-methylsulfonyl) phenyl]-3-trifluoro-methyl-5-[(4-fluoro)phenyl]pyrazole (SC58125; 10 μM) and by the antioxidant trolox (30 μM). In addition, it was observed that COX-2 expression was increased 12 to 24 h after IGF-I treatment. Preincubation of cortical cultures with IGF-I increased arachidonic acid (AA)-induced cytotoxicity, and AA increased Zn2+ toxicity, which suggested the involvement of COX activity in these cellular responses. Moreover, enhanced COX-2 activity led to a decrease in the cell’s reducing power, as indicated by a gradual depletion of intracellular GSH. Cortical neurons pretreated with IGF-I and then Zn2+ showed consistently enhanced reactive oxygen species production, which was repressed by NS-398 and SC58125. Cortical neurons treated with Zn2+ and then AA displayed the increased ROS production, which was also suppressed by NS-398 and SC58125. These results suggest that COX-2 is an endogenous factor responsible for the IGF-I.induced potentiation of Zn2+ toxicity and that enhanced COX-2 activity leads to a decrease in the cell’s reducing power and an increase in ROS accumulation in primary cortical cultures.

ISSN 

0026-895X

Link 

http://dx.doi.org/10.1124/mol.66.3.

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)