Fong J C, Kao Y S, Tsai H, Ho L T
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, ROC.
Cell Signal. 2001 Jul;13(7):491-7. doi: 10.1016/s0898-6568(01)00174-7.
The mechanism of enhancing glucose transport by prolonged endothelin-1 (ET-1) treatment of 3T3-L1 adipocytes was examined. Western and Northern blot analyses indicated that ET-1 increased the amount of both GLUT1 protein and mRNA. The degradation rate of GLUT1 mRNA as measured in the presence of actinomycin D, nevertheless, was not significantly altered by ET-1. Whereas various inhibitors for distinct signalling pathways were tested, only the mitogen-activated protein kinase (MAPK) kinase inhibitor, PD98059, was found to decrease significantly the enhancing effect of ET-1. Similar extent of inhibition was observed in cells pretreated with pertussis toxin (PT). Immunoblot analysis revealed that ET-1 may stimulate a transient phosphorylation of p42/p44 MAPK and both PT and PD98059 inhibited this stimulation. In addition, the effect of ET-1 on GLUT1 mRNA accumulation was inhibited by PD98059 and cycloheximide, implying that a trans-activation was involved. Taken together, these results suggest that ET-1 may induce GLUT1 gene expression by a MAPK-dependent mechanism.
