ABSTRACT
An effector of tissue stress of hepatocytes, prodigiozan-dependent comuton (PDC), provokes deenergiezation of liver mitochondria, preloaded by Ca2+ ions. In this case a decrease of membrane potential (MP) and Ca2+ efflux by cyclosporine A sensitive mechanism of megapore is observed. If megapore is blocked by cyclosporin A, protonofor FCCP provoked decrease of MP and Ca2+ efflux by cyclosporin A-insensitive mechanism. It is shown that PDC increases resistance of mitochondria to mentioned protonofor action by inhibition of both these effects. An inhibitory action of PDC is realized by K+ and NADH-dependent mechanism. The effector of hepatocyte tissue stress, prodigiozan-dependent comuton (PDC), evokes deenergizing liver mitochondria preloaded with Ca2+, both membrane potential (MP) decrease and Ca2+ release in according to cyclosporine A-sensitive mechanism of megapore being observed. If megapore is blocked by cyclosporin A, protonophore FCCP reduces of MP and Ca2+ release in according to cyclosporin A-insensitive mechanism. PDC is shown to increase the resistance of mitochondria against protonophore action mentioned above by means of inhibition of both these effects. Inhibitory action of PDC is realized due to both K+ and NADH-dependent mechanism. Protective effect takes place only in intact mitochondria of these cells providig (on condition that) its megapore mechanism is not activated. Moreover, the results obtained are evidence of PDC can function as protector due to intensification of energy generation in damaged.
Subject(s)
Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology , Mitochondria, Liver/drug effects , Prodigiozan/pharmacology , Proton Ionophores/pharmacology , Animals , Calcium/metabolism , Cyclosporine/pharmacology , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria, Liver/metabolism , Protective Agents/pharmacology , RatsABSTRACT
Endotoxine activated Kupfer cells release into the intercellular space several mediators which act directly on hepatocytes as well as via stellet cells. In both cases Kupfer cells downregulate hepatocytes as a part of paracrine system. However, downregulated part of liver parenchyma might be extended by several mechanisms. The first one is release of vasoconstrictors from activated Kupfer cells which stimulate stellet cells contraction. This effect may also be achieved by formation of hypermetabolicfocuses by Kupffer cells mediators with further activation of hepatocyte-hepatocyte interactions based on the principle of cell competition for oxygen in the intercellular space. Regulatory influence of activated Kupfer cells may be spread in liver parenchyma with participation of the mechanism of intratissue hepatocyte-hepatocyte interactions which also realize tissue stress reaction.
Subject(s)
Hepatocytes/cytology , Hepatocytes/physiology , Kupffer Cells/cytology , Kupffer Cells/physiology , Liver/cytology , Animals , Calcium/metabolism , Humans , Liver/drug effects , Liver/physiology , Prodigiozan/pharmacology , Reactive Oxygen Species/metabolismABSTRACT
Various aspects of protective and damaging influences of endotoxin-activated Kupffer cells on hepatocytes are discussed. Requests for protective subcellular mechanism activated by Kupffer cells mediators were formulated. Two possible mechanisms of activated Kupffer cells protective influence on hepatocytes which satisfy these requests are considered. One of them may operate via hepatocyte non-specific reaction to damage initiated by Kupffer cells mediators. Another one may work through activation of endotoxin-dependent tissue stress mechanism in hepatocytes. The data confirm the development of non-specific reaction to damage and the mechanism of tissue stress realized by means of tissue-specific effector in hepatocytes under endotoxin-activated Kupffer cells influence.
Subject(s)
Cytoprotection/physiology , Endotoxins/metabolism , Hepatocytes/physiology , Kupffer Cells/physiology , Cell Communication , Enzyme Activation , Humans , Inflammation Mediators/metabolism , Intercellular Signaling Peptides and Proteins/metabolismABSTRACT
Current concepts of mechanisms of hypermetabolic states in the body and its selected organs are discussed. Special attention is given to hepatic processes and changes of energy metabolism in hypermetabolic hepatocytes. It is shown that hypermetabolic cells have properties characteristic of the metabolism stimulation phase in cells showing a non-specific reaction to an injury. Differences between cellular hypermetabolism and stimulated metabolism in an injured cell are considered. It is hypothesized that hypermetabolism at the cellular level may be regarded as a stably prolonged phase of stimulated metabolism related to the cell non-specific reaction to an injury.
Subject(s)
Allostasis , Energy Metabolism , Metabolic Networks and Pathways , Stress, Physiological , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Liver/metabolism , Liver/pathology , Metabolism , Oxygen ConsumptionSubject(s)
Calcium Channels/drug effects , Calcium/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Prodigiozan/pharmacology , Animals , Calcium Channels/metabolism , Cations, Divalent/metabolism , Kidney/metabolism , Liver/metabolism , Lung/metabolism , Rats , Ruthenium Red/pharmacologySubject(s)
Liver/metabolism , Mitochondria, Liver/metabolism , Animals , Cell Nucleus/metabolism , Cell-Free System , Cytosol/metabolism , Edetic Acid/pharmacology , Hydrogen-Ion Concentration , Kidney/metabolism , Male , Mitochondria/metabolism , Organ Specificity , Oxidative Phosphorylation , Oxygen Consumption , Prodigiozan/pharmacology , Protease Inhibitors/pharmacology , RatsSubject(s)
Mitochondria, Liver/enzymology , Oxidoreductases/isolation & purification , Animals , Chromatography, Gel , Chromatography, Ion Exchange , Electrophoresis, Polyacrylamide Gel , Intracellular Membranes/enzymology , Kidney/enzymology , Male , Mitochondria/enzymology , Oxidation-Reduction , Oxidoreductases/metabolism , RatsSubject(s)
Calcium/metabolism , Kidney/drug effects , Mitochondria, Liver/drug effects , Mitochondria/drug effects , Animals , Kidney/physiology , Membrane Potentials/drug effects , Mitochondria/physiology , Mitochondria, Liver/physiology , Rats , Rats, Wistar , Temperature , Tissue Extracts/pharmacologySubject(s)
Mitochondria, Liver/drug effects , Oxygen Consumption/drug effects , Animals , Antimycin A/pharmacology , Chromatography, Gel , Chromatography, High Pressure Liquid , Hot Temperature , Male , Mitochondria, Liver/metabolism , Oxidation-Reduction , Potassium Cyanide/pharmacology , Rats , Sodium Cyanide/pharmacology , Succinates/pharmacology , Succinic Acid , Tissue Extracts/pharmacologySubject(s)
Calcium/metabolism , Hot Temperature , Mitochondria, Liver/metabolism , Peptides/metabolism , Adenosine Triphosphatases/metabolism , Animals , Biological Transport/physiology , Kidney/metabolism , Male , Mitochondria/metabolism , Mitochondrial Swelling/physiology , Organ Specificity/physiology , Oxygen Consumption/physiology , Rats , SolubilityABSTRACT
The effect of 2,4-DNP and malonate on tissue-specific uncoupling of oxidative phosphorylation (OP) of rat liver and kidney mitochondria by homologous comutons has been studied. The addition of 2,4-DNP in the presence of comuton induced beta state of comuton regulation. Transfer of liver mitochondria from alpha to beta state also resulted from partial inhibition of succinate dehydrogenase activity of addition of 0.25-0.35 mM malonate. This suggests that the transfer to beta state may be caused by de-energization of mitochondria.
Subject(s)
Dinitrophenols/pharmacology , Kidney/drug effects , Malonates/pharmacology , Mitochondria, Liver/drug effects , Mitochondria/drug effects , Oxidative Phosphorylation/drug effects , Uncoupling Agents/pharmacology , 2,4-Dinitrophenol , Animals , Kidney/metabolism , Male , Mitochondria/metabolism , Mitochondria, Liver/metabolism , Organ Specificity/drug effects , Organ Specificity/physiology , Oxygen Consumption/drug effects , Oxygen Consumption/physiology , RatsABSTRACT
Infusion of phenobarbital and CCl4 was found to induce comuton control of mitochondrial respiration in a liver of starved rats. Comuton regulation of liver mitochondria respiration can be activated either by increase in liver activity or by damage caused by CCl4. The comuton regulation is directly induced by disturbance of energetic homeostasis of liver cells.
Subject(s)
Carbon Tetrachloride/pharmacology , Mitochondria, Liver/drug effects , Phenobarbital/pharmacology , Animals , Kidney/drug effects , Kidney/metabolism , Male , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Mitochondria, Liver/metabolism , Oxidative Phosphorylation/drug effects , Oxygen Consumption/drug effects , Rats , Time FactorsSubject(s)
Kidney/drug effects , Mitochondria, Liver/drug effects , Mitochondria/drug effects , Oxidative Phosphorylation/drug effects , Phosphates/pharmacology , Animals , Dose-Response Relationship, Drug , Kidney/metabolism , Male , Mitochondria/metabolism , Mitochondria, Liver/metabolism , Oligomycins/pharmacology , Organ Specificity/drug effects , Oxygen Consumption/drug effects , Rats , Rotenone/pharmacology , SolubilityABSTRACT
Preincubation of liver mitochondria (Mch) with Ca2+ ions at inorganic phosphate concentration less than I mM in the presence of liver cell soluble phase (CSP) induced rotenone-independent tissue-specific uncoupling of oxidative phosphorylation (beta state of comuton regulation) and rotenone-stimulated tissue-specific uncoupling (gamma state of comuton regulation). The reduction in K+ ion concentration in the incubation medium entirely inhibited the induction of beta state. Tissue-specific stimulation of the rat liver Mch respiration in substrate-containing medium was increased after rotenone addition. Ruthenium red was added to the medium before and after the end of Mch preincubation with Ca2+ in the presence of CSP. The results suggest that limited Ca2+ transport in Mch is necessary for the induction of beta and gamma states of comuton regulation. Ca2+ ejected from Mch also participates in the induction of beta state of comuton regulation. Comuton receptor on the mitochondrial membrane surface is devoid of glyco- and mucoprotein components bound by ruthenium red.