AIM To explore if the inhibitory effect of 3-n-butylphthalide(NBP) on apoptosis induced by transient focal cerebral ischemia in rats is relevant to cortical calcineurin and calpain activities. METHODS The model of cer...AIM To explore if the inhibitory effect of 3-n-butylphthalide(NBP) on apoptosis induced by transient focal cerebral ischemia in rats is relevant to cortical calcineurin and calpain activities. METHODS The model of cerebral ischemia-reperfusion was used. The activities of the two enzymes were measured by using biochemical methods. RESULTS DL -NBP and D -NBP 20 mg·kg -1 were found to significantly reduce ischemia ipsilateral cortical calcineurin and calpain activities. However, L -NBP 20 mg·kg -1 showed no obvious effect. CONCLUSION The anti-apoptotic effect of NBP may be relevant to its inhibition of calcineurin and calpain activities in focal cerebral ischemia rats.展开更多
Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial in...Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia,reperfusion and postischemic structural remodelling.The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains.Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria.Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria.Calpain inhibition can prevent or attenuate myocardial injury during ischemia,reperfusion,and in later stages of myocardial infarction.展开更多
Aging is a popular method used by meat industry for improving the sensory attributes of meat.Despite the advent of many novel technologies,aging has not lost its charm and is still widely used commercially as a post-m...Aging is a popular method used by meat industry for improving the sensory attributes of meat.Despite the advent of many novel technologies,aging has not lost its charm and is still widely used commercially as a post-mortem intervention for tenderization.Aging improves the tenderness of meat through disruption of the muscle structure by intracellular proteolytic systems.Muscles undergo various molecular changes that cause proteolysis of key myofibrillar and cytoskeletal proteins,disrupting the overall integrity of muscle cells.Although several endogenous proteolytic systems are capable of post-mortem proteolysis,a great body of scientific evidence supports a major role for the calpain system.Calpains are intracellular calcium-dependent cysteine proteases found in most eukaryotes.At least three calpains(μ-and m-calpains and calpain 3)and calpastatin,their specific endogenous inhibitor,are found in muscle.They are known to be involved in the proteolysis of functionally relevant structural proteins such as the myofibrillar proteins and cytoskeletal anchorage complexes.These ubiquitous proteases are also present in mitochondria and play important roles in a variety of pathophysiological conditions including apoptotic and necrotic cell death phenomena.This review discusses the role and contribution of the calpain system and the factors that influence calpain activity during aging.展开更多
Cysteine proteases continue to provide validated targets for treatment of human diseases.In neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and c...Cysteine proteases continue to provide validated targets for treatment of human diseases.In neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and cathepsins.The reactive,active-site cysteine provides specificity for many inhibitor designs over other families of proteases,such as aspartate and serine;however,a)inhibitor strategies often use covalent enzyme modification,and b)obtaining selectivity within families of cysteine proteases and their isozymes is problematic.This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders;the latter focus providing an interesting query for the contemporary assumptions that irreversible,covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.展开更多
文摘AIM To explore if the inhibitory effect of 3-n-butylphthalide(NBP) on apoptosis induced by transient focal cerebral ischemia in rats is relevant to cortical calcineurin and calpain activities. METHODS The model of cerebral ischemia-reperfusion was used. The activities of the two enzymes were measured by using biochemical methods. RESULTS DL -NBP and D -NBP 20 mg·kg -1 were found to significantly reduce ischemia ipsilateral cortical calcineurin and calpain activities. However, L -NBP 20 mg·kg -1 showed no obvious effect. CONCLUSION The anti-apoptotic effect of NBP may be relevant to its inhibition of calcineurin and calpain activities in focal cerebral ischemia rats.
文摘Calpains are ubiquitous non-lysosomal Ca2+-dependent cysteine proteases also present in myocardial cytosol and mitochondria.Numerous experimental studies reveal an essential role of the calpain system in myocardial injury during ischemia,reperfusion and postischemic structural remodelling.The increasing Ca2+-content and Ca2+-overload in myocardial cytosol and mitochondria during ischemia and reperfusion causes an activation of calpains.Upon activation they are able to injure the contractile apparatus and impair the energy production by cleaving structural and functional proteins of myocytes and mitochondria.Besides their causal involvement in acute myocardial dysfunction they are also involved in structural remodelling after myocardial infarction by the generation and release of proapoptotic factors from mitochondria.Calpain inhibition can prevent or attenuate myocardial injury during ischemia,reperfusion,and in later stages of myocardial infarction.
文摘Aging is a popular method used by meat industry for improving the sensory attributes of meat.Despite the advent of many novel technologies,aging has not lost its charm and is still widely used commercially as a post-mortem intervention for tenderization.Aging improves the tenderness of meat through disruption of the muscle structure by intracellular proteolytic systems.Muscles undergo various molecular changes that cause proteolysis of key myofibrillar and cytoskeletal proteins,disrupting the overall integrity of muscle cells.Although several endogenous proteolytic systems are capable of post-mortem proteolysis,a great body of scientific evidence supports a major role for the calpain system.Calpains are intracellular calcium-dependent cysteine proteases found in most eukaryotes.At least three calpains(μ-and m-calpains and calpain 3)and calpastatin,their specific endogenous inhibitor,are found in muscle.They are known to be involved in the proteolysis of functionally relevant structural proteins such as the myofibrillar proteins and cytoskeletal anchorage complexes.These ubiquitous proteases are also present in mitochondria and play important roles in a variety of pathophysiological conditions including apoptotic and necrotic cell death phenomena.This review discusses the role and contribution of the calpain system and the factors that influence calpain activity during aging.
文摘Cysteine proteases continue to provide validated targets for treatment of human diseases.In neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and cathepsins.The reactive,active-site cysteine provides specificity for many inhibitor designs over other families of proteases,such as aspartate and serine;however,a)inhibitor strategies often use covalent enzyme modification,and b)obtaining selectivity within families of cysteine proteases and their isozymes is problematic.This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders;the latter focus providing an interesting query for the contemporary assumptions that irreversible,covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.
