Although it is known that hormones, growth factors and integrin promote hepatocyte proliferation in liver regeneration (LR) through ERK1/2 signalling pathway, reports about regulating processes of its intracellular paths in hepatocytes of LR are limited. This study aims at exploring which paths of ERK1/2 signalling pathway participate in the regulation of rat LR, especially in hepatocyte proliferation, and how they do so. In all, 14 paths and 165 genes are known to be involved in ERK1/2 signalling pathway. Of them, 161 genes are included in Rat Genome 230 2.0 Array. This array was used to detect expression changes of genes related to ERK1/2 signalling pathway in isolated hepatocytes of rat LR, showing that 60 genes were related to hepatocytes of LR. In addition, bioinformatics and systems biology methods were used to analyse the roles of 14 above paths in regenerating hepatocytes. We found that three paths, RTK→SHC→GRB2/SOS→RAS→RAF, IntegrinΒ→FAK→RAC→PAK→RAF and GΒγ→PI3KΒγ→RAC→PAK→RAF, promoted the G1 phase progression of hepatocytes by activating ERK1/2. A further four paths, Gq→PLCΒ→PKC→SRC/PYK2→GRB2/SOS→RAS→RAF, RTK→PLCγ→PKC→SRC/PYK2→GRB2/SOS→RAS→RAF, IntegrinΒ→FAK/SRC→GRB2/SOS→RAS→RAF and IntegrinΒ→FAK→RAC→PAK→RAF, advanced the cell progression of S phase and G(2)/M checkpoint by activating ERK1/2, and so did PP1/2→Mek1/2 by decreasing the negative influence on ERK1/2. At the late phase of LR, Gαs→AC→EPAC→Rap1→Raf blocked hepatocyte proliferation by decreasing the activity of ERK1/2 and so did PP1/2→Mek1/2. In summary, 60 genes and 8 paths of ERK1/2 signalling pathway regulated hepatocyte proliferation in rat LR.
Reactive oxygen species (ROS) are known to be involved in many neurodegenerative diseases. This study assessed the effect of Claulansine F, a new carbazole isolated from Clausena lansium, on sodium nitroprusside (SNP)-treated rat pheochromocytoma PC12 cells. First, it was found that Claulansine F showed more potential on inhibiting the programmed death of PC12 cells than edaravone by cell viability, morphologic observation, and flow cytometric analysis. Further results also showed that Claulansine F attenuated the production of total intracellular ROS formation and lipid peroxidation in PC12 cells, inhibited the mitochondrial membrane potential (MMP) loss, and prevented the programmed cell death event via the P53/Bcl-2 family pathway. Its protective effect was likely medicated by the hydroxyl radical (·OH) scavenging ability, as it appeared to be not involved in the natural antioxidant system. These results suggested a promising potential for Claulansine F as a ROS scavenger in pathologies, where an oxidative stress is involved.
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