Hepatitis C virus nonstructural protein 5A inhibits tumor necrosis factor-alpha-mediated apoptosis in Huh7 cells.

Autor: Miyasaka, Yuka, Enomoto, Nobuyuki, Kurosaki, Masayuki, Sakamoto, Naoya, Kanazawa, Nobuhiko, Kohashi, Takahiro, Ueda, Eri, Maekawa, Shinya, Watanabe, Hideki, Izumi, Namiki, Sato, Chifumi, Watanabe, Mamoru
Předmět:
Zdroj: Journal of Infectious Diseases; 11/15/2003, Vol. 188 Issue 10, p1537-1544, 8p
Abstrakt: To analyze the influence of hepatitis C virus nonstructural protein 5A (NS5A) on apoptosis, we established Huh7 cells that stably express NS5A, and induced apoptosis using tumor necrosis factor (TNF)-alpha. The viability of control Huh7 cells was reduced to 40%, compared with untreated cells, after TNF-alpha treatment, whereas that of Huh7-NS5A cells was reduced only to 80%. DNA fragmentation also decreased to <50% in Huh7-NS5A compared with control cells. Nuclear factor-kappaB activation was the same in both cell types, whereas caspase-8, -9, and -3 activity was decreased in Huh7-NS5A cells, compared with control cells, which indicates that the inhibition of caspase-8 activation is responsible for the antiapoptotic effect of the NS5A protein. The coexpression of NS5A did not inhibit apoptosis induced by caspase-8 or Fas-associating death domain protein expression. These findings suggest that the NS5A protein inhibits the apoptotic effect of TNF-alpha upstream of caspase-8 in the apoptosis cascade. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index