RESUMEN
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.
Asunto(s)
Carbonil Cianuro p-Trifluorometoxifenil Hidrazona/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Prodigiozán/farmacología , Ionóforos de Protónes/farmacología , Animales , Calcio/metabolismo , Ciclosporina/farmacología , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias Hepáticas/metabolismo , Sustancias Protectoras/farmacología , RatasRESUMEN
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.
Asunto(s)
Hepatocitos/citología , Hepatocitos/fisiología , Macrófagos del Hígado/citología , Macrófagos del Hígado/fisiología , Hígado/citología , Animales , Calcio/metabolismo , Humanos , Hígado/efectos de los fármacos , Hígado/fisiología , Prodigiozán/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
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.
Asunto(s)
Citoprotección/fisiología , Endotoxinas/metabolismo , Hepatocitos/fisiología , Macrófagos del Hígado/fisiología , Comunicación Celular , Activación Enzimática , Humanos , Mediadores de Inflamación/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismoRESUMEN
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.
Asunto(s)
Alostasis , Metabolismo Energético , Redes y Vías Metabólicas , Estrés Fisiológico , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Hígado/metabolismo , Hígado/patología , Metabolismo , Consumo de OxígenoAsunto(s)
Canales de Calcio/efectos de los fármacos , Calcio/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Prodigiozán/farmacología , Animales , Canales de Calcio/metabolismo , Cationes Bivalentes/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Ratas , Rojo de Rutenio/farmacologíaAsunto(s)
Sustancias de Crecimiento/metabolismo , Macrófagos del Hígado/fisiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Prodigiozán/farmacología , Animales , Pollos , Masculino , Mitocondrias Hepáticas/metabolismo , Especificidad de Órganos , Consumo de Oxígeno , Fagocitosis , RatasAsunto(s)
Hígado/metabolismo , Mitocondrias Hepáticas/metabolismo , Animales , Núcleo Celular/metabolismo , Sistema Libre de Células , Citosol/metabolismo , Ácido Edético/farmacología , Concentración de Iones de Hidrógeno , Riñón/metabolismo , Masculino , Mitocondrias/metabolismo , Especificidad de Órganos , Fosforilación Oxidativa , Consumo de Oxígeno , Prodigiozán/farmacología , Inhibidores de Proteasas/farmacología , RatasAsunto(s)
Mitocondrias Hepáticas/enzimología , Oxidorreductasas/aislamiento & purificación , Animales , Cromatografía en Gel , Cromatografía por Intercambio Iónico , Electroforesis en Gel de Poliacrilamida , Membranas Intracelulares/enzimología , Riñón/enzimología , Masculino , Mitocondrias/enzimología , Oxidación-Reducción , Oxidorreductasas/metabolismo , RatasAsunto(s)
Calcio/metabolismo , Riñón/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Animales , Riñón/fisiología , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias/fisiología , Mitocondrias Hepáticas/fisiología , Ratas , Ratas Wistar , Temperatura , Extractos de Tejidos/farmacologíaAsunto(s)
Mitocondrias Hepáticas/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Animales , Antimicina A/farmacología , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Calor , Masculino , Mitocondrias Hepáticas/metabolismo , Oxidación-Reducción , Cianuro de Potasio/farmacología , Ratas , Cianuro de Sodio/farmacología , Succinatos/farmacología , Ácido Succínico , Extractos de Tejidos/farmacologíaAsunto(s)
Calcio/metabolismo , Calor , Mitocondrias Hepáticas/metabolismo , Péptidos/metabolismo , Adenosina Trifosfatasas/metabolismo , Animales , Transporte Biológico/fisiología , Riñón/metabolismo , Masculino , Mitocondrias/metabolismo , Dilatación Mitocondrial/fisiología , Especificidad de Órganos/fisiología , Consumo de Oxígeno/fisiología , Ratas , SolubilidadRESUMEN
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.
Asunto(s)
Dinitrofenoles/farmacología , Riñón/efectos de los fármacos , Malonatos/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacos , Desacopladores/farmacología , 2,4-Dinitrofenol , Animales , Riñón/metabolismo , Masculino , Mitocondrias/metabolismo , Mitocondrias Hepáticas/metabolismo , Especificidad de Órganos/efectos de los fármacos , Especificidad de Órganos/fisiología , Consumo de Oxígeno/efectos de los fármacos , Consumo de Oxígeno/fisiología , RatasRESUMEN
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.
Asunto(s)
Tetracloruro de Carbono/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Fenobarbital/farmacología , Animales , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Mitocondrias Hepáticas/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Ratas , Factores de TiempoAsunto(s)
Riñón/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Fosforilación Oxidativa/efectos de los fármacos , Fosfatos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Riñón/metabolismo , Masculino , Mitocondrias/metabolismo , Mitocondrias Hepáticas/metabolismo , Oligomicinas/farmacología , Especificidad de Órganos/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Ratas , Rotenona/farmacología , SolubilidadRESUMEN
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.