Adrenaline induces mitochondrial biogenesis in rat liver (original) (raw)
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Redox cycling of adrenaline and adrenochrome catalysed by mitochondrial Complex I
Archives of Biochemistry and Biophysics, 2006
Complex I in bovine heart submitochondrial particles catalyses the NADH-supported generation of superoxide anion; adrenaline is oxidised by superoxide to adrenochrome that, on its hand, is reduced by Complex I, thus establishing a redox cycle that ampliWes the superoxide production. The routes in Complex I for superoxide formation and for adrenochrome reduction appear to be diVerent, since they have a diVerent sensitivity to Complex I inhibitors. The results are discussed in terms of current assays for superoxide detection and of pathologies linked to catecholamine oxidation.
Experimental Cell Research, 1997
The transition from fetus to neonate involves a activity of mitochondria from fetal hepatocytes in primary culture was studied. In the absence of adrena-shift from a relatively anaerobic environment to an line, the respiratory control ratio (RCR) of mitochon-aerobic one. This situation requires the rapid postnadria increased during the first 3 days of culture due to tal acquisition of efficient energy-transducing mitoa decrease in the rate of state 4 respiration. The preschondria. In fact, liver mitochondria reach adult ence of adrenaline in the incubation medium further functional capacity within the first hour of extrauterincreased the mitochondrial RCR through a decrease ine life, as shown by the sharp increase in the respirain the rate of respiration in state 4 and to an increase tory control ratio (RCR) 2 [1] and in the activities of in the respiration rate in state 3. The effect of adrenathe respiratory-chain and of ATP-synthase comline was mimicked by dibutyryl-cAMP, forskolin, and plexes observed during this short period [2]. Postnaisobutyl methyl xanthine. All these compounds intal mitochondrial differentiation is brought about by creased cAMP concentrations, suggesting that cAMP the synergistic action of two main processes, i.e., an may be involved in the effect of adrenaline. The inenhancement of the synthesis of proteins involved crease in intracellular free Ca 2/ concentrations caused in energy transduction [2] and an accumulation of by phenylephrine, vasopressin, or thapsigargin was adenine nucleotides in the mitochondrial matrix [1, also accompanied by an increase in the RCR, sug-3], which occurs shortly after birth [1, 3-5]. gesting that both phenomena are associated. Dibu-It has been suggested that the hormone status of tyryl-cAMP also increased free Ca 2/ concentrations, the newborn probably modulates the rate of adenine suggesting that the effects of cAMP may be mediated nucleotide accumulation either directly or indirectly by free Ca 2/ concentrations. Adrenaline, dibutyrylthrough changes in the cytoplasmic ATP/ADP ratio [3, cAMP, phenylephrine, vasopressin, and thapsigargin 6, 7]. Thus, immediately after birth a sharp increase promoted adenine nucleotide accumulation in mitoin plasma catecholamine concentrations occurs [8-10] chondria; this may be an intermediate step in the actiwhich has been proposed to be responsible for resisvation of mitochondrial respiratory function. These results suggest that the stimulatory effect of adrena-tance to postnatal hypoxia in newborns [9]. It should line on mitochondrial maturation in cultured fetal rat be mentioned that hypoxia may cause a decrease in hepatocytes may be exerted through a mechanism in mitochondrial adenine nucleotide concentrations while which both cAMP and Ca 2/ act as second messengers. exposure to adrenaline would enhance total adenine It is concluded that the effect of adrenaline on mitonucleotide contents in vitro [see 11]. chondrial maturation is exerted by both a-and b-adb-Adrenergic receptor functions are predominant in renergic mechanisms and is mediated by the increase fetal rat liver but their coupling to adenylate cyclase in adenine nucleotide contents of mitochondria. ᭧ 1997 decreases during early neonatal life [12], a-adrenergic Academic Press functions being predominant [see 13] after maturation.
Biochemical Journal, 2004
Changes in the kinetics and regulation of oxidative phosphorylation were characterized in isolated rat liver mitochondria after 2 months of ethanol consumption. Mitochondrial energy metabolism was conceptually divided into three groups of reactions, either producing protonmotive force (∆p) (the respiratory subsystem) or consuming it (the phosphorylation subsystem and the proton leak). Manifestation of ethanol-induced mitochondrial malfunctioning of the respiratory subsystem was observed with various substrates ; the respiration rate in State 3 was inhibited by 27p4 % with succinate plus amytal, by 20p4 % with glutamate plus malate, and by 17p2 % with N,N,Nh,Nhtetramethyl-p-phenylenediamine\ascorbate. The inhibition of the respiratory activity correlated with the lower activities of cytochrome c oxidase, the bc " complex, and the ATP synthase in mitochondria of ethanol-fed rats. The block of reactions consuming the ∆p to produce ATP (the phosphorylating subsystem)
H2O2 Production and Response to Stress Conditions by Mitochondrial Fractions from Rat Liver
2002
Rat liver mitochondria, in different steps of the maturation process, were resolved by differential centrifugation at 1000g (M 1), 3000g (M 3), and 10,000g (M 10), and their characteristics determining susceptibility to stress conditions were investigated. Some parameters did not show gradual changes in the transition from M 10 to M 1 fraction because of the contamination of the M 10 fraction by microsomes and damaged mitochondria with relatively high lipid content. The highest and lowest rates of O 2 consumption and H 2 O 2 production were exhibited by M 1 and M 10 fractions, respectively. Vitamin E and coenzyme Q levels were significantly higher in M 10 than in M 1 fraction, whereas whole antioxidant capacity was not significantly different. The degree of oxidative damage to lipids and proteins was higher in M 1 and not significantly different in M 3 and M 10 fractions. The order of susceptibility to both oxidative challenge and Ca 2+-induced swelling was M 1 > M 3 > M 10. It seems that the Ca 2+-induced swelling is due to permeabilization of oxidatively altered inner membrane and leads to discard mitochondria with high ROS production. If, as previous reports suggest, mitochondrial damage is initiating stimulus to mitochondrial biogenesis, the susceptibility of the M 1 mitochondria to stressful conditions could be important to regulate cellular ROS production. In fact, it should favor the substitution of the oldest ROS-overproducing mitochondria with neoformed mitochondria endowed with a smaller capacity to produce free radicals.
Effects of Endotoxin and Catecholamines on Hepatic Mitochondrial Respiration
Inflammation, 2009
Catecholamines are frequently used in sepsis, but their interaction with mitochondrial function is controversial. We incubated isolated native and endotoxin-exposed swine liver mitochondria with either dopamine, dobutamine, noradrenaline or placebo for 1 h. Mitochondrial State 3 and 4 respiration and their ratio (RCR) were determined for respiratory chain complexes I, II and IV. All catecholamines impaired glutamate-dependent RCR (p=0.046), predominantly in native mitochondria. Endotoxin incubation alone induced a decrease in glutamate-dependent RCR compared to control samples (p=0.002). We conclude that catecholamines and endotoxin impair the efficiency of mitochondrial complex I respiration in vitro.
Chronic ketamine administration impairs mitochondrial complex I in the rat liver
Life Sciences, 2013
Aim: Ketamine can induce hepatotoxicity which has been suggested to be dependent on mitochondrial impairment. This study investigated the long-term effects of chronic low-dose ketamine on liver mitochondrial function, oxidative stress parameters, liver histology and glycogen content. Main methods: Adult rats were administered with saline or ketamine (5 or 10 mg/kg) twice a day for a fourteenday period in order to mimic chronic treatments. Effects between groups were compared ten days after the treatment had ended. Liver mitochondrial function was monitored in isolated mitochondrial extracts through evaluation of respiration parameters and activity of respiratory complexes, as well as oxidative stress, through lipid peroxidation, protein oxidation and superoxide dismutase activity. The hepatic histology and liver glycogen content were also evaluated. Key findings: Ketamine groups showed a decreased evolution in body weight gains during the treatment period. Ketamine had no effect either on serum liver enzymes or on the oxidative stress parameters of liver mitochondria. Ketamine decreased the hepatic glycogen content, inhibited mitochondrial complex I and oxygen consumption when glutamate-malate substrate was used. Significance: These findings reflect a long-term mitochondrial bioenergetic deterioration induced by ketamine, which may explain the increased susceptibility of some patients to its prolonged or repeated use.
… Supplemental Series A …, 2008
Respiration parameters of liver mitochondria (MCh) in rats fed with amaranth seed oil for 3 weeks have been evaluated. Thirty minutes before decapitation, adrenaline was injected intraperitoneally at a low dose (350 µ g/kg body weight) to both control and experimental animals. It was shown that in animals that were injected with adrenaline and did not receive oil, the rate of phosphorylating respiration increased by 32% and phosphorylation time decreased by 22% upon oxidation of succinate; upon oxidation of α-ketoglutarate in the presence of the succinate dehydrogenase inhibitor malonate, phosphorylating respiration was activated by 23%. The respiration of MCh upon oxidation of succinate + glutamate and α-ketoglutarate in the absence of malonate was not affected by adrenaline. The intake of oil markedly activated almost all parameters of mitochondrial respiration in experimental rats upon oxidation of all above-listed substrates in both coupled and uncoupled MCh. However, phosphorylation time was close to the control value (upon oxidation of succinate) or increased (upon oxidation of α-ketoglutarate in the presence and absence of malonate). The injection of adrenaline to animals receiving oil did not affect the oil-activated respiration of MCh oxidizing the substrates used; however, phosphorylation time in all groups of animals decreased. Ca 2+ capacity of MCh in rats receiving amaranth oil did not change. Thus, our data show that feeding of rats with amaranth oil activates mitochondrial respiration and prevents MCh hyperactivation induced by adrenaline.
Molecular and Cellular Biochemistry, 2011
Hepatic encephalopathy is an important cause of morbidity and mortality in patients with severe hepatic failure. This disease is clinically characterized by a large variety of symptoms including motor symptoms, cognitive deficits, as well as changes in the level of alertness up to hepatic coma. Acetaminophen is frequently used in animals to produce an experimental model to study the mechanisms involved in the progression of hepatic disease. The brain is highly dependent on ATP and most cell energy is obtained through oxidative phosphorylation, a process requiring the action of various respiratory enzyme complexes located in a special structure of the inner mitochondrial membrane. In this context, the authors evaluated the activities of mitochondrial respiratory chain complexes in the brain of rats submitted to acute administration of acetaminophen and treated with the combination of N-acetylcysteine (NAC) plus deferoxamine (DFX) or taurine. These results showed that acetaminophen administration inhibited the activities of complexes I and IV in cerebral cortex and that the treatment with NAC plus DFX or taurine was not able to reverse this inhibition. The authors did not observe any effect of acetaminophen administration on complexes II and III activities in any of the structures studied. The participation of oxidative stress has been postulated in the hepatic encephalopathy and it is well known that the electron transport chain itself is vulnerable to damage by reactive oxygen species. Since there was no effect of NAC + DFX, the effect of acetaminophen was likely to be due to something else than oxidative stress.