Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under...Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however,excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research,coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.展开更多
Objective:To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan(葫芦巴丸,HLBW)on the testis of diabetic rats.Methods:Twenty-four male Wistar rats(160–180 g)were randomly divided into 3 groups ...Objective:To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan(葫芦巴丸,HLBW)on the testis of diabetic rats.Methods:Twenty-four male Wistar rats(160–180 g)were randomly divided into 3 groups according to a random number table,including a control group(n=8),diabetic group(n=8),and HLBW group(n=8).Diabetic rat model was established by high-fat-diet administration and single intravenous injection of streptozotocin(26 mg/kg).Then HLBW granule was administrated for 12 weeks.Fasting blood glucose and insulin levels as well as serum total testosterone level and testicular testosterone content were examined.Oxidative stress markers in both serum and testis were tested.Meanwhile,testicular morphology was observed under hematoxylin and eosin(HE)and the ultrastructure of Leydig cell was observed by electron microscope.The superoxide anion level was detected by DHE,and TUNEL-positive cells of testis was evaluated by TUNEL assay.The gene and protein expression of protein kinase C(PKCα),phosphorylated PKCα(P-PKCα)and P47 phox in testicular tissues were determined by quantitative RT-PCR analysis and Western bolt analysis.Results:Compared with the diabetic group,HLBW treatment significantly reduced the fasting glucose levels and increased the levels of fasting insulin and testosterone in serum(P<0.01).HLBW administration also reduced the levels of reactive oxygen species(ROS)in plasma and alleviated the damage of oxidative stress in the testis of diabetic rats.Additionally,HLBW down-regulated the protein and m RNA levels of PKCα,P-PKCαand P47 phox in testicular tissues.Conclusion:HLBW may attenuate the oxidative stress in the testis of diabetic rats via PKCα/NAPDH oxidase signaling pathway.展开更多
基金partially supported by Merit Review Award(I01RX-001964-01)from the US Department of Veterans Affairs Rehabilitation Research and Development Service(to YD)the National Natural Science Foundation of China(81501141)+1 种基金Beijing New Star of Science and Technology Program of China(xx2016061)Beijing Tongzhou District Financial Fund,and Scientific Research Common Program of Beijing Municipal Commission of Education,China(KM201610025028)(to XG)
文摘Nicotinamide adenine dinucleotide phosphate oxidase(NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however,excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis. Moreover, recent studies have established that glucose, as a NOX substrate, plays a vital role in the pathogenesis of reperfusion injury. Thus, NOX inhibition has the potential to mitigate the deleterious impact of hyperglycemia on stroke. In this paper, we provide an overview of this research,coupled with a discussion of its implications for the development of NOX inhibition as a strategy for the treatment of ischemic stroke. Both inhibition using apocynin, as well as the prospect of developing more specific inhibitors based on what is now understood of the biology of NOX assembly and activation, will be highlighted in the course of our discussion.
基金Supported by the National Natural Science Foundation of China(No.81703886,81273683)。
文摘Objective:To explore the protective effect and the underlying mechanism of Hu-Lu-Ba-Wan(葫芦巴丸,HLBW)on the testis of diabetic rats.Methods:Twenty-four male Wistar rats(160–180 g)were randomly divided into 3 groups according to a random number table,including a control group(n=8),diabetic group(n=8),and HLBW group(n=8).Diabetic rat model was established by high-fat-diet administration and single intravenous injection of streptozotocin(26 mg/kg).Then HLBW granule was administrated for 12 weeks.Fasting blood glucose and insulin levels as well as serum total testosterone level and testicular testosterone content were examined.Oxidative stress markers in both serum and testis were tested.Meanwhile,testicular morphology was observed under hematoxylin and eosin(HE)and the ultrastructure of Leydig cell was observed by electron microscope.The superoxide anion level was detected by DHE,and TUNEL-positive cells of testis was evaluated by TUNEL assay.The gene and protein expression of protein kinase C(PKCα),phosphorylated PKCα(P-PKCα)and P47 phox in testicular tissues were determined by quantitative RT-PCR analysis and Western bolt analysis.Results:Compared with the diabetic group,HLBW treatment significantly reduced the fasting glucose levels and increased the levels of fasting insulin and testosterone in serum(P<0.01).HLBW administration also reduced the levels of reactive oxygen species(ROS)in plasma and alleviated the damage of oxidative stress in the testis of diabetic rats.Additionally,HLBW down-regulated the protein and m RNA levels of PKCα,P-PKCαand P47 phox in testicular tissues.Conclusion:HLBW may attenuate the oxidative stress in the testis of diabetic rats via PKCα/NAPDH oxidase signaling pathway.
