Role of cAMP in regulation of activity of acid hydrolases of rat heart and liver during ischemia and after recirculation

Molchanova, L. V.; Nickulina, Svetlana E.; Иванова, Т. М.; Ivanov, A.; Polyskova, Elvira D.

doi:10.1016/0300-9572(91)90034-v

Cited by 8 publications

(4 citation statements)

References 18 publications

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“…De Duve and Wattiaux (1966) first reported that the lethal cell injury occurs by the release of hydrolytic enzymes from damaged lysosomes. Spreading of hydrolytic enzymes into the cytoplasm by the lysosomal membrane injury or rupture, was confirmed in both heart (Brachfeld, 1969;Ichihara et al, 1987;Molchanova et al, 1991) and brain (White et al, 1992;Chan, 1996) ischemic injuries. The translocation of cathepsin B from lysosomes to cytosol and nucleus was confirmed also in the bile salt-induced and tumor necrosis factor (TNF)-triggered hepatic apoptosis Guicciardi et al, 2001).…”

Section: Discussionmentioning

confidence: 93%

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates

et al. 2003

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ABSTRACT:Because of the paucity of primate experimental models, the precise molecular mechanism of ischemic neuronal death remains unknown in humans. This study focused on nonhuman primates to determine which cascade necrosis or apoptosis is predominantly involved in the development of delayed (day 5) neuronal death in the hippocampal CA1 sector undergoing 20 min ischemia. We investigated expression, activation, and/or translocation of -calpain, lysosome-associated membrane protein-1 (LAMP-1), caspase-3, and caspase-activated DNase (CAD), as well as morphology of the postischemic CA1 neurons and DNA electrophoresis pattern. Immunoblotting showed sustained (immediately after ischemia until day 5) and maximal (day 3) activation of -calpain. The immunoreactivity of activated -calpain became remarkable as coarse granules at lysosomes on day 2, while it translocated throughout the perikarya on day 3. The immunoreactivity of LAMP-1 also showed a dynamic and concomitant translocation that was maximal on days 2-3, indicating calpain-mediated disruption of the lysosomal membrane after ischemia. In contrast, immunoblotting demonstrated essentially no increase in the activated caspase-3 at any time points after ischemia, despite upregulation of pro-caspase-3. Although expression of CAD was slightly upregulated on day 1 or 2, or both, it was much less compared with lymph node or intestine tissues. Furthermore, light and electron microscopy showed eosinophilic coagulation necrosis and membrane disruption without apoptotic body formation, while DNA electrophoresis did not show a ladder pattern, but rather a smear pattern. Sustained calpain activation and the resultant lysosomal rupture, rather than CAD-mediated apoptosis, may cause ischemic neuronal necrosis in primates.

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Section: Discussionmentioning

confidence: 93%

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates

et al. 2003

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“…More recent findings support these findings and documented that release of lysosomal iron and its uptake into mitochondria through the calcium uniporter can act synergistically with oxidant stress to promote the MPT and cell death [42]. Since hepatic ischemia and reperfusion can trigger lysosomal instability [63,64] and oxidant stress can be produced by mitochondria or extracellularly by leukocytes, which then triggers an intracellular stress, the combination of the lysosomal iron and ROS can induce the MPT and necrosis [42]. The critical importance of mitochondrial dysfunction and the MPT in determining cell death during hepatic warm and cold ischemia–reperfusion injury has been demonstrated by the protective effects of cyclophilin D inhibitors [61,62].…”

Section: Mechanisms Of Oxidant Stress-induced Liver Injurymentioning

confidence: 84%

Current strategies to minimize hepatic ischemia–reperfusion injury by targeting reactive oxygen species

Jaeschke

Woolbright

2012

Transplantation Reviews

269

239

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Ischemia–reperfusion is a major component of injury in vascular occlusion both during liver surgery and during liver transplantation. The pathophysiology of hepatic ischemia–reperfusion includes a number of mechanisms including oxidant stress that contribute to various degrees to the overall organ damage. A large volume of recent research has focused on the use of antioxidants to ameliorate this injury, although results in experimental models have not translated well to the clinic. This review focuses on critical sources and mediators of oxidative stress during hepatic ischemia–reperfusion, the status of current antioxidant interventions, and emerging mechanisms of protection by preconditioning. While recent advances in regulation of antioxidant systems by Nrf2 provide interesting new potential therapeutic targets, an increased focus must be placed on more in-depth mechanistic investigations in hepatic ischemia–reperfusion injury and translational research in order to refine current strategies in disease management.

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“…The reanimation complex included indirect massage of the heart and artificial ventilation of the lungs with room air through an intubator inserted in the trachea. The efficacy of reanimation was assessed by the time needed for the recovery of heart work, spontaneous respiration, and corneal reflexes [10,12]. The control group consisted of animals decapitated synchronously with experimental groups after light ether narcosis.…”

Section: Methodsmentioning

confidence: 99%

“…The permeability of lysosomal membranes and the activity of acid hydrolases in the cytosol of hepatic and myocardial cells have been shown to be increased in the early postischemic and postreanimation period [2,3]. The detected relationship between the intracellular cAMP concentration and the state of lysosomal membranes during postischemic recovery permits one to hypothesize a cAMP-mediated mechanism regulating lysosomal activity [6,10].In this research we investigated the relationship between the rate of endogenous phosphorylation of proteins in the lysosomal fraction of rat liver and heart and the level of cAMP during the early postreanimation period. …”

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confidence: 99%

Endogenous phosphorylation of lysosomal proteins of rat heart and liver in the early postreanimation period

et al. 1995

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The lysosomal fraction isolated in a PercoU gradient from rat liver and heart after 30 min of the postreanimation period following a 5-min heart arrest stimulated incorporation of 32p in total lysosomal protein. Addition of cAMP and protein inhibitor of cAMP-dependent protein kinase changed the rate of phosphorylation. Endogenous phosphorylation of total lysosomal protein in the postreanimation period was reduced in the heart and increased in the liver. This may be due to a change in the intracellular level of cAMP, which fell in the heart and rose in the liver. Key Words: lysosomes; cAMP-dependent phosphorylation; postreanimation period; heart; liverThe lysosomal enzymes play an important role in the development of destructive changes in the heart and liver tissues during both hypoxia and ischemia, as well as during postischemic rehabilitation [8]. The permeability of lysosomal membranes and the activity of acid hydrolases in the cytosol of hepatic and myocardial cells have been shown to be increased in the early postischemic and postreanimation period [2,3]. The detected relationship between the intracellular cAMP concentration and the state of lysosomal membranes during postischemic recovery permits one to hypothesize a cAMP-mediated mechanism regulating lysosomal activity [6,10].In this research we investigated the relationship between the rate of endogenous phosphorylation of proteins in the lysosomal fraction of rat liver and heart and the level of cAMP during the early postreanimation period.

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Role of cAMP in regulation of activity of acid hydrolases of rat heart and liver during ischemia and after recirculation

Cited by 8 publications

References 18 publications

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates

Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates

Current strategies to minimize hepatic ischemia–reperfusion injury by targeting reactive oxygen species

Endogenous phosphorylation of lysosomal proteins of rat heart and liver in the early postreanimation period

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