Figure 4.

A cAMP analog, or an activator of adenylyl cyclase Forskolin, or NECA down regulates p53 and Rb through down regulation of Rac1 and decreased activation of p38 MAPK in the HSC. LX-2 cells were treated for 2 days, and 10 days cultured activated primary rat HSC were treated for 5 days with 8-Bromo-cAMP (1mM) or, Forskolin (50 μM) or NECA (10 μM) in presence or absence of PKA inhibitor 12–14 amide (myristoylated; 10 μM) or H-89 dihydrochloride hydrate (25 μM). (A) Western blot analysis of p53, Rb, Rac1, and p44/42 MAPK levels in the 2 days treated LX-2 cells. (B) Western blot analysis of p53, Rb, Rac1, and p44/42 MAPK levels in the 5 days treated activated rat primary HSC. (C) Summary of adenosine receptor A_2A mediated signaling in the process of senescence in HSC.