XXXX transferases P1/P2 regulate the timing of signaling pathway activations and cell cycle progression during @entity19 liver regeneration.

@entity1896 @entity71433 @entity13765 @entity19 @entity71432 @entity10433 @entity2041 @entity777 @entity11953 @entity14032 @entity842 @entity11319 @entity71434 @entity37362 @entity9829 @entity637 @entity8837 @entity12156
@entity2041 transferases (GST) are phase II enzymes catalyzing the detoxification of endogenous noxious compounds and xenobiotics. They also regulate phosphorylation activities of MAPKinases in a catalytic-independent manner. Previous studies have demonstrated the regulation of @entity14032 -dependent pathway by @entity71432 . Considering the crucial role of @entity14032 in the early steps of the hepatocyte cell cycle, we sought to determine whether @entity71432 were essential for hepatocyte proliferation following partial hepatectomy (PH). Using a conventional double knockout @entity19 model for the @entity71433 and @entity71434 genes, we found that the lack of @entity71433 reduced the rate of DNA replication and mitotic index during the first wave of hepatocyte proliferation. The lowered proliferation was associated with the decrease in @entity637 and @entity777 plasma concentrations, reduced hepatic @entity13765 expression and delayed and/or altered activation of @entity10433 , @entity14032 and @entity8837 signaling pathways. In addition, the expression and/or activation of cell cycle regulators such as @entity1896 , @entity11953 , @entity11319 and @entity12156 was postponed demonstrating that the absence of @entity71432 delayed the entry into and progression through the G1 phase of the cell cycle and impaired the synchrony of proliferation in hepatocytes following PH. Furthermore, while @entity14032 and its downstream targets @entity9829 and @entity37362 were activated during the early steps of the liver regeneration in wild-type animals, the constitutively active @entity14032 found in the quiescent liver of @entity71432 knockout @entity19 underwent a decrease in its activity after PH. Transient induction of antioxidant enzymes and @entity842 synthase were also delayed or repressed during the regenerative response. Altogether our results demonstrate that @entity71432 are a critical regulators of hepatocyte proliferation in the initial phases of liver regeneration.
