Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for ...Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.展开更多
Uric acid(UA)-lowering bioactive peptides have emerged as promising alternatives to synthetic drugs owing to their favorable safety profile,efficacy,and bioavailability.This study investigated the anti-hyperuricemic(H...Uric acid(UA)-lowering bioactive peptides have emerged as promising alternatives to synthetic drugs owing to their favorable safety profile,efficacy,and bioavailability.This study investigated the anti-hyperuricemic(HUA)mechanisms of xanthine oxidase(XOD)-inhibitory peptides derived from Harpadon nehereus hydrolysate(HNPH).Three potent uric acid(UA)-reducing peptides were identified:FLH(FH3),FGKF(FF4),and IWHHTF(IF6).These peptides altered the secondary structure of XOD and bind to it through hydrogen bonding and hydrophobic interactions,thereby inhibiting XOD catalytic activity.Compared with FH3 and IF6,FF4 showed the strongest XOD inhibitory activity after in vitro digestion and was selected for further in vivo experiments.FF4 reduced UA levels by inhibiting hepatic UA-synthesizing enzymes,upregulating UA transporter ABCG2,and downregulating GLUT9.It alleviated inflammation and oxidative stress in HUA mice livers/kidneys,reducing pathological damage and inflammatory infiltration.FF4 also mitigated UA-induced HK-2 cell damage by regulating ROS and NLRP3 inflammatory pathways.These findings support marine-derived peptides as novel HUA therapeutics,offering alternatives to conventional drugs.展开更多
文摘Calpains are calcium-activated cysteine proteases. There are two main isoforms of calpain that are ubiquitously expressed in tissues, calpain μ or calpain 1, which requires micromolar Ca<sup>2+</sup> for activation, and calpain or 2, which requires millimolar Ca<sup>2+</sup> for activation. The presence of other calpains is tissue specific. Atherosclerosis (AS) is an important risk factor for cerebral infarction, coronary heart disease and peripheral vascular disease. It was originally thought that AS was caused by impaired lipid metabolism. This research briefly reviewed Calpain Family, the structure and activation mechanism of calpain1, Calpains in the pathogenesis of atherosclerosis, NLRP3 structural characteristics and activation, ROS/NLRP3 inflammasome activation mechanism and ROS/NLRP3 inflammasome in atherosclerosis. The research showed that the Calpain-1 may play an important role in mitochondrial ROS/NLRP3 inflammasome in atherosclerosis.
基金supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.LQN25C200011.
文摘Uric acid(UA)-lowering bioactive peptides have emerged as promising alternatives to synthetic drugs owing to their favorable safety profile,efficacy,and bioavailability.This study investigated the anti-hyperuricemic(HUA)mechanisms of xanthine oxidase(XOD)-inhibitory peptides derived from Harpadon nehereus hydrolysate(HNPH).Three potent uric acid(UA)-reducing peptides were identified:FLH(FH3),FGKF(FF4),and IWHHTF(IF6).These peptides altered the secondary structure of XOD and bind to it through hydrogen bonding and hydrophobic interactions,thereby inhibiting XOD catalytic activity.Compared with FH3 and IF6,FF4 showed the strongest XOD inhibitory activity after in vitro digestion and was selected for further in vivo experiments.FF4 reduced UA levels by inhibiting hepatic UA-synthesizing enzymes,upregulating UA transporter ABCG2,and downregulating GLUT9.It alleviated inflammation and oxidative stress in HUA mice livers/kidneys,reducing pathological damage and inflammatory infiltration.FF4 also mitigated UA-induced HK-2 cell damage by regulating ROS and NLRP3 inflammatory pathways.These findings support marine-derived peptides as novel HUA therapeutics,offering alternatives to conventional drugs.
