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TNFα induced NF-κB activation in skeletal muscle L6 cells is regulated by cell glutathione status
CERTAIN ASPECTS OF MEMBRANE DAMAGE DURING HEPATITIS V. Kipiani, N. Kipiani, T. San&i&e, M. Topuridze, N. Pkhaladze
TNFa INDUCED NF-KB ACTIVATION IN SKELETAL MUSCLE L6 CELLS IS REGULATED BY CELL GLUTATHIONE STATUS S. Khanna, S. Roy, A. Z. Reznick, L. Packer, C. K. Sen Dept. of Physiology, University of Kuopio, 7021 I Kuopio, Finland; University of California at Berkeley, CA 94720
Tbilisi State Medical University, Tbilisi, Georgia
By the method of electronic paramagnetic resonance (EPR) have been studied pammagnetic centres of liver and blood with experimental hepatitis in rabbits. As follows from results of experiments in hepatitis activation of lipid peroxidation processes and damage of membrane structural integrity accompanied by decreasing of body antioxidant potential take place. It should be emphasised, that increasing the contents of xanthinoxidase and nitric oxide in liver represents the hallmark of activation of Ca*+-dependent NO-synthetase and hypoxanthinoxidase system. Accumulation of cytosolic Ca*+ would be contributed with alteration of membrane permeability due to peroxidation of phospholipids within them, as well as ischemia due to disturbance of electronic transport chain in mitochondria and lack of macroergic compounds synthesis. In its turn nitric oxide, ubiquinon, xanthinoxidase, as well as Mn*+ ions are powerful initiators of free radical oxidation. So is circled the circus vicious contributing to irreversible destruction of hepatic tissue.
TNFa is implicated in several skeletal muscle pathologies including muscle wasting of cachexia. Muscle wasting and conditions other such as physical exercise and immobilization are also associated with disturbances in muscle glutathione status. We observed that TNFa L6 potently induced transient NF-KB activation in myoblasts. In GSH depleted cells, TNFa induced NF-KB activation was potentiated suggesting that such activation is sensitive to cellular GSH. Because this activation was inhibited by the antioxidant pyrrolidinedithiocarbamate (PDTC) the involvement of reactive oxygen in this activation system seems likely. NF-I& activation in L6 cells was also observed in response to direct H,Oz treatment. Results from GSSG reductase inhibited cells suggest that GSSG may participate in, but is not required for, TNFa induced NF-KB activation. The inhibitory effect of PDTC on NF-KB activation correlated with its effect on ICAh4-1 expression suggesting that this GSH status modifying agent not only influenced nuclear translocation of NF-KB proteins but also regulated KB dependent transcription. GSH regulated CAM expression may have remarkable implication in exercise associated leukocyte margination in skeletal muscle.
DAILY RHYTHMIC VARIATIONS IN YOUNG MICE LIVER ANTIOXIDANT SYSTEM AND SERUM NITRITE IN RESPONSE TO EXERCISE N. &h~, G. Sasmaz, E. Gelir, C. 2. Gorgun, U. Hodoglugil, H. Zengil, D. Erbas, and N. Bukan Deparments of Biochemistry, Physiology and Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey
The influence of extreme work load on ion distribution in the With this purpose content of ions Na, K, and Mg in venous blood erythrocytes and plasma 01 Ca healthy, uot trained mn in relation IO heavy exrrcise (230 W, I 0 min. vcloergoineter). was determined usmg sp~cfrophotoin~tn. It was revealed significant change of ion on cycle distribution in blood wrthm I mm after work ergometer. Blood plasma, similar by electrolyte content lo mterccllular tluid, was characterized by increased on 7 and 8% concentrations of Na and K but reduced on 5 and I7On lwels of Ca and Mg corespondingly. At that time the values of Ne and Mg concentrations differ from their nonnsl magnitudes for healtby resting persons. deviations Such promote unfavorable shifts of ion balance in all cells of organism. According to mtasurwxnts the erythrocytc cells during the first minure after heax?; \vork load had considerable heightened on 55, 90 and 20”~ concrntratlona of Na. Ca and Mg correspondingly, These displacements depend on mcressmg the membran penneabiility and reduction of active ion transport due to fall in cell encrgetics and accumulation of mcmranedamaging me~abolites inside and outside the 4s. Shown ion profound overloads in erythrocytes lead to diminution of the physical lwfonnancc and rising time period of it restorotlon. blood \vasinvestigated.
This study was aimed to show daily rhythmic variations in the antioxidant system influenced by physical exercise. 4 week-old locally bred male Swiss albino mice were subjected to light exercise (5min, lOm/min, 0% incline treadmill running) at 4 hour intervals for 24 hours. Animals were killed by decapitation under ether anaesthesia and the livers were removed immediately. determined by were levels nitrite Serum cherniluminescence. ANOVA and post hoc Student Newman Keuls tests on the results indicated significant daily biorhythms in liver GPX activities and GSH levels in the control and the exercise groups (p
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TNFa INDUCED NF-KB ACTIVATION IN SKELETAL MUSCLE L6 CELLS IS REGULATED BY CELL GLUTATHIONE STATUS S. Khanna, S. Roy, A. Z. Reznick, L. Packer, C. K. Sen Dept. of Physiology, University of Kuopio, 7021 I Kuopio, Finland; University of California at Berkeley, CA 94720
Tbilisi State Medical University, Tbilisi, Georgia
By the method of electronic paramagnetic resonance (EPR) have been studied pammagnetic centres of liver and blood with experimental hepatitis in rabbits. As follows from results of experiments in hepatitis activation of lipid peroxidation processes and damage of membrane structural integrity accompanied by decreasing of body antioxidant potential take place. It should be emphasised, that increasing the contents of xanthinoxidase and nitric oxide in liver represents the hallmark of activation of Ca*+-dependent NO-synthetase and hypoxanthinoxidase system. Accumulation of cytosolic Ca*+ would be contributed with alteration of membrane permeability due to peroxidation of phospholipids within them, as well as ischemia due to disturbance of electronic transport chain in mitochondria and lack of macroergic compounds synthesis. In its turn nitric oxide, ubiquinon, xanthinoxidase, as well as Mn*+ ions are powerful initiators of free radical oxidation. So is circled the circus vicious contributing to irreversible destruction of hepatic tissue.
TNFa is implicated in several skeletal muscle pathologies including muscle wasting of cachexia. Muscle wasting and conditions other such as physical exercise and immobilization are also associated with disturbances in muscle glutathione status. We observed that TNFa L6 potently induced transient NF-KB activation in myoblasts. In GSH depleted cells, TNFa induced NF-KB activation was potentiated suggesting that such activation is sensitive to cellular GSH. Because this activation was inhibited by the antioxidant pyrrolidinedithiocarbamate (PDTC) the involvement of reactive oxygen in this activation system seems likely. NF-I& activation in L6 cells was also observed in response to direct H,Oz treatment. Results from GSSG reductase inhibited cells suggest that GSSG may participate in, but is not required for, TNFa induced NF-KB activation. The inhibitory effect of PDTC on NF-KB activation correlated with its effect on ICAh4-1 expression suggesting that this GSH status modifying agent not only influenced nuclear translocation of NF-KB proteins but also regulated KB dependent transcription. GSH regulated CAM expression may have remarkable implication in exercise associated leukocyte margination in skeletal muscle.
DAILY RHYTHMIC VARIATIONS IN YOUNG MICE LIVER ANTIOXIDANT SYSTEM AND SERUM NITRITE IN RESPONSE TO EXERCISE N. &h~, G. Sasmaz, E. Gelir, C. 2. Gorgun, U. Hodoglugil, H. Zengil, D. Erbas, and N. Bukan Deparments of Biochemistry, Physiology and Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey
The influence of extreme work load on ion distribution in the With this purpose content of ions Na, K, and Mg in venous blood erythrocytes and plasma 01 Ca healthy, uot trained mn in relation IO heavy exrrcise (230 W, I 0 min. vcloergoineter). was determined usmg sp~cfrophotoin~tn. It was revealed significant change of ion on cycle distribution in blood wrthm I mm after work ergometer. Blood plasma, similar by electrolyte content lo mterccllular tluid, was characterized by increased on 7 and 8% concentrations of Na and K but reduced on 5 and I7On lwels of Ca and Mg corespondingly. At that time the values of Ne and Mg concentrations differ from their nonnsl magnitudes for healtby resting persons. deviations Such promote unfavorable shifts of ion balance in all cells of organism. According to mtasurwxnts the erythrocytc cells during the first minure after heax?; \vork load had considerable heightened on 55, 90 and 20”~ concrntratlona of Na. Ca and Mg correspondingly, These displacements depend on mcressmg the membran penneabiility and reduction of active ion transport due to fall in cell encrgetics and accumulation of mcmranedamaging me~abolites inside and outside the 4s. Shown ion profound overloads in erythrocytes lead to diminution of the physical lwfonnancc and rising time period of it restorotlon. blood \vasinvestigated.
This study was aimed to show daily rhythmic variations in the antioxidant system influenced by physical exercise. 4 week-old locally bred male Swiss albino mice were subjected to light exercise (5min, lOm/min, 0% incline treadmill running) at 4 hour intervals for 24 hours. Animals were killed by decapitation under ether anaesthesia and the livers were removed immediately. determined by were levels nitrite Serum cherniluminescence. ANOVA and post hoc Student Newman Keuls tests on the results indicated significant daily biorhythms in liver GPX activities and GSH levels in the control and the exercise groups (p
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