The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in i...The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.展开更多
Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most imp...Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor γ (PPARγ), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPAR7 agonists are therapeutic agents used in the treatment of type 2 diabetes. This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARγ in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARγ modulators.展开更多
The mechanisms for fine-tuning ABA level related to grape berry ripening remain elusive. Here, transcription analysis showed that the mRNA expression level of 9-cis-epoxycarotenoid dioxygenase gene (VvNCED1) increas...The mechanisms for fine-tuning ABA level related to grape berry ripening remain elusive. Here, transcription analysis showed that the mRNA expression level of 9-cis-epoxycarotenoid dioxygenase gene (VvNCED1) increases first, rapidly in mesocarp before the onset of grape berry ripening. After VvNCED1 peaks its expression level, ABA content increases rapidly in mesocarp coupled with an increase in both soluble sugar content and pH value. On the onset of berry ripening, VvNCED1 transcripts decline rapidly to its lowest point, then increases slightly. Whereas, the mRNA expression level of B-glucosidase gene VvBGI, on the whole, increases constantly during grape berry ripening. During berry de-greening, ABA glucosyltransferase (VvGT) and ABA 8'-hydroxylase (VvCYPI) equilibrate ABA level; during berry coloring-up, VvGT predominantly equilibrates ABA level, namely, the up-regulation of ABA level mainly leads from VvNCED1 and VvBG1 gene high expression; the down-regulation of ABA level leads mainly from VvCYP! transcript level both in ABA content- and developmental phase-dependence manner. In conclusion, our main results show that VvNCED1 and VvBG1 genes are closely related to grape berry ripening.展开更多
Orexin-A (OxA) is a key neuropeptide involved in the central control of appetite and the maintenance of energy homeostasis, as well as in the regulation of glycemia. In the present study, OxA receptors, OXtR and OX2...Orexin-A (OxA) is a key neuropeptide involved in the central control of appetite and the maintenance of energy homeostasis, as well as in the regulation of glycemia. In the present study, OxA receptors, OXtR and OX2R were identified to be highly expressed in porcine hepatocytes. 100 nM OxA could rapidly stimulate the glucose output of porcine hepatocytes in 10min. Primary hepatocytes treated by 1 nM-500 nM OxA for 24 h significantly increase the released glucose and the concentration of albumin, total bile acids and triglyceride in the supernatant. The mRNA expression level of such gluconeogenesis and fat mobilization related genes as acetyl-coA carboxylase, glycogen phosphorylase, fatty acid translocase and phosphoenolpyrurate carboxykinase were also up-regulated accordingly. The results first demonstrated that OxA had direct effect on the hepatic glucose and lipid metabolism, which was an aspect for OxA to exert its maintenance function of energy homeostasis.展开更多
文摘The WNK kinases are a recently discovered family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis. Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia. This review focuses on the recent evidence elucidating the structure of the kinase domain of WNK1 and functions of these kinases in normal and disease physiology. Their functions have implications for understanding the biochemical mechanism that could lead to the retention or insertion of proteins in the plasma membrane. The WNK kinases may be able to influence ion homeostasis through its effects on synaptotagmin function.
基金supported by the Etat de Vaud and the Swiss National Science Foundation.
文摘Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor γ (PPARγ), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPAR7 agonists are therapeutic agents used in the treatment of type 2 diabetes. This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARγ in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARγ modulators.
基金This study is supported by China National Nattu-al Science Foundation (Project 31040006) and Beijing Natural Science Foundation and Scientific Research Key Program of Beijing Commission of Education (NO. KZ200910020001).
文摘The mechanisms for fine-tuning ABA level related to grape berry ripening remain elusive. Here, transcription analysis showed that the mRNA expression level of 9-cis-epoxycarotenoid dioxygenase gene (VvNCED1) increases first, rapidly in mesocarp before the onset of grape berry ripening. After VvNCED1 peaks its expression level, ABA content increases rapidly in mesocarp coupled with an increase in both soluble sugar content and pH value. On the onset of berry ripening, VvNCED1 transcripts decline rapidly to its lowest point, then increases slightly. Whereas, the mRNA expression level of B-glucosidase gene VvBGI, on the whole, increases constantly during grape berry ripening. During berry de-greening, ABA glucosyltransferase (VvGT) and ABA 8'-hydroxylase (VvCYPI) equilibrate ABA level; during berry coloring-up, VvGT predominantly equilibrates ABA level, namely, the up-regulation of ABA level mainly leads from VvNCED1 and VvBG1 gene high expression; the down-regulation of ABA level leads mainly from VvCYP! transcript level both in ABA content- and developmental phase-dependence manner. In conclusion, our main results show that VvNCED1 and VvBG1 genes are closely related to grape berry ripening.
基金Acknowledgements: This work was supported by the Joint Funds of the National Natural Science Foundation of China (No. u0731004), National Natural Science Foundation of China (No. 30871845) and Natural Science Foundation of Guangdong Province of China (No. 07118116).
文摘Orexin-A (OxA) is a key neuropeptide involved in the central control of appetite and the maintenance of energy homeostasis, as well as in the regulation of glycemia. In the present study, OxA receptors, OXtR and OX2R were identified to be highly expressed in porcine hepatocytes. 100 nM OxA could rapidly stimulate the glucose output of porcine hepatocytes in 10min. Primary hepatocytes treated by 1 nM-500 nM OxA for 24 h significantly increase the released glucose and the concentration of albumin, total bile acids and triglyceride in the supernatant. The mRNA expression level of such gluconeogenesis and fat mobilization related genes as acetyl-coA carboxylase, glycogen phosphorylase, fatty acid translocase and phosphoenolpyrurate carboxykinase were also up-regulated accordingly. The results first demonstrated that OxA had direct effect on the hepatic glucose and lipid metabolism, which was an aspect for OxA to exert its maintenance function of energy homeostasis.