Investigation that protein oxidation to the formation of advanced glycation end products(AGEs)after chicken myofibrillar protein glycation is limited.Models of protein oxidation induced by different concentrations of ...Investigation that protein oxidation to the formation of advanced glycation end products(AGEs)after chicken myofibrillar protein glycation is limited.Models of protein oxidation induced by different concentrations of hydroxyl radicals(·OH)were developed after the chicken myofibrillar protein mild glycation(MPG).Results exhibited that levels of AGEs and surface hydrophobicity(H_(0))steadily increased with the a ddition of h ydrogen peroxide(H_(2)O_(2))concentration.However,levels of s ulfhydryl group,free amino group,and particle size gradually decreased with the H_(2)O_(2)concentration.The protein carbonyl value increased in H_(2)O_(2)concentration until 10 mmol/L.Pearson's correlation indicated that MPG structure modification(unfolding and degradation)induced by protein oxidation were significantly positively correlated with AGEs concentration(P<0.05).Finally,a mechanism was proposed to hypothesize t he effect of protein oxidation on the formation of AGEs under MPG conditions.展开更多
Accumulation of plasma advanced oxidation protein products(AOPPs) promotes progression of proteinuria and glomerulo-sclerosis.To investigate the molecular basis of AOPPs-induced proteinuria,normal Sprague-Dawley rats ...Accumulation of plasma advanced oxidation protein products(AOPPs) promotes progression of proteinuria and glomerulo-sclerosis.To investigate the molecular basis of AOPPs-induced proteinuria,normal Sprague-Dawley rats were treated with AOPPs-modified rat serum albumin.The expression of glomerular podocyte slit diaphragm(PSD)-associated proteins,nephrin and podocin,was significantly decreased coincident with the onset of albuminuria in rats treated with AOPPs.Chronic inhibi-tion of NADPH oxidase by apocynin prevented down-regulation of nephrin and podocin and decreased albuminuria in AOPPs-challenged rats.This suggested that accumulation of AOPPs promotes proteinuria,possibly via down-regulating the expression of PSD-associated proteins.展开更多
Background Advanced oxidation protein products （AOPPs） are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs en...Background Advanced oxidation protein products （AOPPs） are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 （MCP-1） is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells （VSMCs）.展开更多
Background:As accelerators and products of the progression of chronic kidney disease(CKD),advanced oxidation protein products(AOPPs)affect the function of the liver.Huang Gan granules(HGGs)are commonly used to prevent...Background:As accelerators and products of the progression of chronic kidney disease(CKD),advanced oxidation protein products(AOPPs)affect the function of the liver.Huang Gan granules(HGGs)are commonly used to prevent the progression of CKD,but the pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs in CKD remain unknown.Objective:To investigate the influence and its molecular mechanism of AOPPs on the in vivo pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs.Methods:We constructed 5/6 nephrectomised(5/6 nx),adenine-induced(adenine)and AOPP-treated rat models.After oral administration of HGG,the concentrations of aloe-emodin,emodin,rhein,and chrysophanol in the plasma samples were detected by high-performance liquid chromatography(HPLC),and their pharmacokinetics were analysed with the PKSolver software.The plasma concentrations of IL-6 and TNF-αare detected by enzyme linked immunosorbent assay(ELISA).The RT-PCR was performed in the HepG2 cells to explore the effect of TNF-αand IL-6 on the mRNA expression of CYP1A2 and CYP3A4.Result:The results showed that the method was suitable for the quantification of four anthraquinones in plasma and excreta samples with satisfactory linear(R R^(2)>0.9931),precision(<9.4%)and accuracy(±10%).In 5/6 nx,adenine and AOPPs-treated rats,the concentrations of TNF-αand IL-6 were increased.In 5/6 nx and adenine rats,the pharmacokinetic parameters(t_(1/2),MRT_(0-∞)and AUC_(0-∞))of aloe-emodin,emodin,rhein,and chryso-phanol were,respectively,significantly increased and correlated with the concentration of AOPPs.In AOPPs-treated rats,the concentration of AOPPs was significantly increased and the pharmacokinetic parameters of four anthraquinones were also increased.Conclusion:In summary,inflammatory cytokine production may be one of the important causes in AOPPs’regulat-ing the pharmacokinetic of aloe-emodin,emodin,rhein,and chrysophanol in the CKD rats.Studies of aloe-emodin,emodin,rhein,and chrysophanol in CKD facilitate the appropriate prescription of HGGs in the clinical.展开更多
基金supported by National Key R&D Program of China(2021YFD2100104)griculture Research System of China(CARS-41-Z)+2 种基金Science and Technology Project of Nanjing City(202002040)Jiangsu Province Policy Guidance Program(BX2020008)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX21_0579),China。
文摘Investigation that protein oxidation to the formation of advanced glycation end products(AGEs)after chicken myofibrillar protein glycation is limited.Models of protein oxidation induced by different concentrations of hydroxyl radicals(·OH)were developed after the chicken myofibrillar protein mild glycation(MPG).Results exhibited that levels of AGEs and surface hydrophobicity(H_(0))steadily increased with the a ddition of h ydrogen peroxide(H_(2)O_(2))concentration.However,levels of s ulfhydryl group,free amino group,and particle size gradually decreased with the H_(2)O_(2)concentration.The protein carbonyl value increased in H_(2)O_(2)concentration until 10 mmol/L.Pearson's correlation indicated that MPG structure modification(unfolding and degradation)induced by protein oxidation were significantly positively correlated with AGEs concentration(P<0.05).Finally,a mechanism was proposed to hypothesize t he effect of protein oxidation on the formation of AGEs under MPG conditions.
基金supported by the National Natural Science Foundation of China (Grant Nos 30830056 and 30830056)the National Basic Research Program of China (Grant No 2006CB503904) to Dr HOU FanFan+1 种基金the National Natural Science Foundation of China (Grant No 30971382)the Natural Science Foundation of Guangdong Province (Grant No 06024402) to Dr LIANG Min
文摘Accumulation of plasma advanced oxidation protein products(AOPPs) promotes progression of proteinuria and glomerulo-sclerosis.To investigate the molecular basis of AOPPs-induced proteinuria,normal Sprague-Dawley rats were treated with AOPPs-modified rat serum albumin.The expression of glomerular podocyte slit diaphragm(PSD)-associated proteins,nephrin and podocin,was significantly decreased coincident with the onset of albuminuria in rats treated with AOPPs.Chronic inhibi-tion of NADPH oxidase by apocynin prevented down-regulation of nephrin and podocin and decreased albuminuria in AOPPs-challenged rats.This suggested that accumulation of AOPPs promotes proteinuria,possibly via down-regulating the expression of PSD-associated proteins.
文摘Background Advanced oxidation protein products （AOPPs） are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 （MCP-1） is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells （VSMCs）.
基金supported by Guangdong Science and Technology Program(No.2015B020211006)the Technology Project of Guangzhou City in China(No.201604020137)+2 种基金Shenzhen Foundation of Science and Technology(No.JCYJ20190814112205770)Research Foundation of Shenzhen Hospital of Southern Medical University(No.PY2021YM03)the Project of Traditional Chinese Medicine Bureau of Guangdong Province(No.20221273).
文摘Background:As accelerators and products of the progression of chronic kidney disease(CKD),advanced oxidation protein products(AOPPs)affect the function of the liver.Huang Gan granules(HGGs)are commonly used to prevent the progression of CKD,but the pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs in CKD remain unknown.Objective:To investigate the influence and its molecular mechanism of AOPPs on the in vivo pharmacokinetics of aloe-emodin,emodin,rhein,and chrysophanol in HGGs.Methods:We constructed 5/6 nephrectomised(5/6 nx),adenine-induced(adenine)and AOPP-treated rat models.After oral administration of HGG,the concentrations of aloe-emodin,emodin,rhein,and chrysophanol in the plasma samples were detected by high-performance liquid chromatography(HPLC),and their pharmacokinetics were analysed with the PKSolver software.The plasma concentrations of IL-6 and TNF-αare detected by enzyme linked immunosorbent assay(ELISA).The RT-PCR was performed in the HepG2 cells to explore the effect of TNF-αand IL-6 on the mRNA expression of CYP1A2 and CYP3A4.Result:The results showed that the method was suitable for the quantification of four anthraquinones in plasma and excreta samples with satisfactory linear(R R^(2)>0.9931),precision(<9.4%)and accuracy(±10%).In 5/6 nx,adenine and AOPPs-treated rats,the concentrations of TNF-αand IL-6 were increased.In 5/6 nx and adenine rats,the pharmacokinetic parameters(t_(1/2),MRT_(0-∞)and AUC_(0-∞))of aloe-emodin,emodin,rhein,and chryso-phanol were,respectively,significantly increased and correlated with the concentration of AOPPs.In AOPPs-treated rats,the concentration of AOPPs was significantly increased and the pharmacokinetic parameters of four anthraquinones were also increased.Conclusion:In summary,inflammatory cytokine production may be one of the important causes in AOPPs’regulat-ing the pharmacokinetic of aloe-emodin,emodin,rhein,and chrysophanol in the CKD rats.Studies of aloe-emodin,emodin,rhein,and chrysophanol in CKD facilitate the appropriate prescription of HGGs in the clinical.
