The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate(FPP) or geranylgeranyl pyrophosphate(GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess Caa X motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase(GGPPS) catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.
Vascular remodeling is a pathological condition with structural changes of blood vessels.Both inside-out and outside-in hypothesis have been put forward to describe mechanisms of vascular remodeling.An integrated model of these two hypotheses emphasizes the importance of immune cells such as monocytes/macrophages,T cells,and dendritic cells.These immune cells are at the center stage to orchestrate cellular proliferation,migration,and interactions of themselves and other vascular cells including endothelial cells(ECs),vascular smooth muscle cells(VSMCs),and fibroblasts.These changes on vascular wall lead to inflammation and oxidative stress that are largely responsible for vascular remodeling.Mineralocorticoid receptor(MR)is a classic nuclear receptor.MR agonist promotes inflammation and oxidative stress and therefore exacerbates vascular remodeling.Conversely,MR antagonists have the opposite effects.MR has direct roles on vascular cells through non-genomic or genomic actions to modulate inflammation and oxidative stress.Recent studies using genetic mouse models have revealed that MR in myeloid cells,VSMCs and ECs all contribute to vascular remodeling.In conclusion,data in the past years have demonstrated that MR is a critical control point in modulating vascular remodeling.Studies will continue to provide evidence with more detailed mechanisms to support this notion.
Non-alcoholic fatty liver disease（NAFLD） is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus（T2DM）, dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1（GLP-1） analogues and dipeptidyl peptidase-4（DPP-4） inhibitors were widely used to treat T2 DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor（GLP-1R） is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride（TG） content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and m RNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.
