Mol Cell Biochem. 2009 May 3; Sun X, Zhang XD, Cheng G, Hu YH, Wang HYHepatic stellate cells (HSCs) play an important role in the development of hepatic fibrosis. Heat shock protein 90 (Hsp90) is essential for the maturation and activity of a varied group of proteins involved in signal transduction and cell cycle regulation. In this study, we found that two Hsp90 inhibitors, VER-49009 and its analog VER-49009M, inhibited the proliferation of hepatic stellate cell line CFSC cells, and both of them induced G2 phase arrest in CFSC cells. Akt expression was decreased by the treatment of Hsp90 inhibitors in CFSC cells. Based on these findings, we propose that the inhibition of Hsp90 might be a rational approach in the prevention of liver fibrosis.
Tyrosine nitration by peroxynitrite can affect signal transduction pathways involving tyrosine phosphorylation.
The present study was undertaken to investigate the effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells. We show here that exposure of HepG2 cells to peroxynitrite led to a dose-dependent increase in tyrosine nitration of cellular proteins, mainly membrane and nuclear proteins.
Furthermore, peroxynitrite induced differential responses in tyrosine phosphorylation of membrane proteins as well as cytosolic proteins according to peroxynitrite concentrations used.
Our findings indicate at low concentrations peroxynitrite upregulates the insulin signaling and may operate as a signaling molecule, but at higher concentrations peroxynitrite downregulates the insulin signaling and may be involved in insulin resistance, suggesting peroxynitrite plays a dual role in regulation of the insulin signaling.
"Effects of peroxynitrite-induced protein tyrosine nitration on insulin-stimulated tyrosine phosphorylation in HepG2 cells."
Mol Cell Biochem. 2009 May 8; Zhou J, Li H, Zeng J, Huang K
Curr Top Med Chem. 2009; 9(4): 348-61Ye D, Wang J, Yu K, Zhou Y, Jiang H, Chen K, Liu HPotassium ion (K(+)) channels consist of a ubiquitous family of membrane proteins that play critical roles in a wide variety of physiological processes, such as the regulation of neuronal excitability, muscle contraction, cell proliferation, and insulin secretion. Due to their pivotal functions in biological systems, K(+) channels have long been attractive targets for the rational drug design on the basis of their structures and interaction mechanisms. Various small-molecular compounds and toxins have been discovered to act as K(+) channel modulators. In the present review, we will first briefly discuss current knowledge of the structures and functions of K(+) channels, and then review the recent strategies for the discovery of K(+) channel modulators, focusing especially on the virtual screening approaches and chemical synthesis technologies.
Neuroscience. 2009 May 11; Rui L, Mei G, Guifen Q, Tiantai Z, Xi L, Jian Y, Guanhua DLuteolin is an important member of the flavonoid family. It exhibits strongly anti-inflammatory, anti-oxidant and phytoestrogen-like activities. In the present study, we examined the anti-amnesic and protective effects of luteolin against Ass(25-35) -induced toxicity in mice. Mice were given an intracerebroventricular injection of aggregated Ass(25-35) peptide. The learning and memory impairments, ultrastructural changes of cerebral cortex, cerebrovascular dysfunction and neuronal changes were detected after oral administration of luteolin continuously for 8 days. Our results demonstrate that oral administration of luteolin for 8 days for those Ass(25-35) -induced amnesic mice conferred robust neurovascular protection in Ass(25-35) -induced amnesia, involving the improvement of the spatial learning and memory capabilities, the modulation of microvascular function, the increase of regional cerebral blood flow values, the clearance of ROS, the improvement of cholinergic neuronal system, and the raise of BNDF level and its receptor TrkB expression in cerebral cortex.
