Hormones and liver mitochondria: Effects of growth hormone and thyroxine on respiration, fluorescence of 1-anilino-8-naphthalene sulfonate and enzyme activities of complex I and II of submitochondrial particles

Maddaiah, V.T.; Clejan, Sanda; Palekar, Anil G.; Collipp, P.J.

doi:10.1016/0003-9861(81)90234-4

Cited by 29 publications

(14 citation statements)

References 26 publications

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“…The detection of GH in mitochondria raised the question of its functional relevance for the regulation of oxidative phosphorylation. Consistently, it has been shown that GH regulates the oxidative function of liver cell mitochondria in GH-treated hypophysectomized rats [20,21,22,23]. More recently, we reported that GH stimulates cellular respiration after binding to its receptor through initiating both a GH-dependent signal transduction pathway and internalization of GH and GHR through a caveolar-dependent pathway [24].…”

Section: Introductionmentioning

confidence: 54%

“…Based on the data presented here and on previous observations which reported the capacity of GH to partially restore hypophysectomy-induced alterations at the level of protein synthesis [43,44], cytochrome concentration, enzymatic activity and the rate of protein turnover [18] as well as the improvement of liver mitochondrial respiration [20,21,22,23], we suggest that GH can be now added to the list of mitochondria regulating-competent hormones.…”

Section: Discussionmentioning

confidence: 99%

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Growth Hormone Internalization in Mitochondria Decreases Respiratory Chain Activity

et al. 2009

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Growth hormone (GH) is a signaling molecule regulating cell proliferation, differentiation and metabolism via activation of specific cell surface receptors and subsequent triggering of signal transduction pathways. This is associated with GH/GH receptor internalization and accumulation of GH in several subcellular compartments, including mitochondria. To assess the functional relevance of such mitochondrial accumulation, we first confirmed the occurrence of mitochondrial GH uptake ex vivo as early as 10 min after ¹²⁵I-GH injection to the rats. We next showed that intact ¹²⁵I-GH accumulates in mitochondrial fractions in vitro in a specific, rapid and saturable manner with an apparent affinity (K_d) of 1.44 nM. At the electron-microscopic level, immunoreactive GH density within mitochondria increased after in vitro hormone incubation, without any modification of the sub-mitochondrial distribution pattern. The presence of GH in the inter-membrane space and at the inner membrane seen by electron microscopy was confirmed by SDS-PAGE and autoradiography after mitochondrial fractioning thus suggesting the involvement of GH in the respiration control. To test this hypothesis further, we performed polarographic and spectrophotometric assays on isolated mitochondria. These assays pointed to a direct, selective and dose-dependent effect of GH on the inhibition of succinate dehydrogenase and cytochrome C oxidase activities. The latter inhibition was in contrast with indirect, GH receptor-initiated stimulation of cytochrome C oxidase activity observed in GH-treated whole BRL cells transfected to express this receptor. Altogether, these data show that GH is specifically imported in mitochondria, where it operates a direct metabolic effect, independently of cell surface receptors and signal transduction.

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Section: Introductionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Growth Hormone Internalization in Mitochondria Decreases Respiratory Chain Activity

et al. 2009

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“…Hyperthyroidy was responsible for a decrease in the ⌬⌿ mito as assessed in intact cells, which is in favor of a primary increase in slippage responsible for a decreased membrane potential. Several reports in the literature have investigated the relationship between mitochondrial membrane potential and hyperthyroidy, and the results are conflicting, probably depending on the experimental tool used for assessing membrane potential in intact cells (5,8,(51)(52)(53)(54). This could also explain the decrease in the overall coupling in oxidative phosphorylation (ATP/O ratio) when oxidative phosphorylation flux increases (Figs.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Respiratory Chain Adjustment to Cellular Energy Demand

Nogueira

Rigoulet

Piquet

et al. 2001

Journal of Biological Chemistry

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Because adaptation to physiological changes in cellular energy demand is a crucial imperative for life, mitochondrial oxidative phosphorylation is tightly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequence on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper-and hypothyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol intoxication) we found that the increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O 2 /min/mg dry cells) was tightly correlated with total mitochondrial cytochrome content, expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxidase; while total cytochrome content increased 2-fold (from 0.341 ؎ 0.021 to 0.821 ؎ 0.024 nmol/mg protein), cytochrome oxidase increased 10-fold (from 0.020 ؎ 0.002 to 0.224 ؎ 0.006 nmol/mg protein). This modification was associated with a decrease in the overall efficiency of the respiratory chain. Since cytochrome oxidase is well recognized for slippage between redox reactions and proton pumping, we suggest that this dramatic increase in cytochrome oxidase is responsible for the decrease in the overall efficiency of respiratory chain and, in turn, of ATP synthesis yield, linked to the adaptive increase in oxidative phosphorylation capacity.In aerobic living systems, oxidative phosphorylation activity can vary widely to adequately match ATP synthesis to energy demand according to physiological or pathological conditions. In contrast to short-term adaptation, which relies only on a flux modulation through every functional unit of mitochondrial oxidative phosphorylation, chronic adaptation to various rates of ATP utilization can also be achieved by modifying the number of these functional units (mitogenesis). Indeed, in the light of the large physiological variations in ATP turnover observed in living systems, it is highly probable that the amount of enzymes involved in the oxidative phosphorylation pathway plays a significant role. Recently the trade-off between rate and yield of ATP synthesis in heterotrophic organisms has been highlighted as a possible major mechanism of cooperation and competition involved in the evolutionary aspects of energy metabolism (1).By investigating the effect on the yield of ATP synthesis (ATP/O) 1 after acute modulations of the flux through the oxidative phosphorylation pathway in yeast mitochondria, it has been shown that the decrease in flux was accompanied by an increase in efficiency when the flux was limited by substrate supply (2-4). Conversely, no change in ATP/O was observed when the oxidative phosphorylation flux was modulated by the inhibition of ATP synthesis (oligomycin) (2-4). Hence, depending on the mechanism permitting to modulate the flux through the respiratory chain, different cons...

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“…Their diagnosis had been confirmed by the typical clinical course, characteristic physical findings, which included pelvifemoral weakness and calf pseudohypertrophy, family history, raised serum levels of creatinine kinase (CK), lactate dehydrogenase (LDH), and serum glutamate oxaloacetate transaminase (SGOT), and abnormal findings on muscle biopsy and electromyography. The ages of these nine children at the time of entry into the study were 5, 6,7,7,8,10,12,12, and 14 years.…”

Section: Methodsmentioning

confidence: 99%

Growth hormone inhibition causes increased selenium levels in Duchenne muscular dystrophy: a possible new approach to therapy.

Collipp¹,

Kelemen²,

Chen³

et al. 1984

Journal of Medical Genetics

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SUMMARY Nine children with Duchenne muscular dystrophy were given Sanorex (mazindol), a growth hormone inhibitor, daily for 6 months. There was no significant change in their muscle function, but there was a significant reduction in weight gain and in levels of growth hormone, somatomedin C, hair zinc, serum zinc, and serum LDH. Selenium and glutathione peroxidase in the serum increased significantly. Thirteen other children with growth hormone deficiency had a significant reduction in hair selenium following growth hormone administration.These results show a significant relationship between growth hormone and selenium nutritional status and confirm our previous reports indicating an effect of growth hormone on zinc nutritional status. It is possible that prolonged therapy with a growth hormone inhibitor would attenuate the course and improve the longevity of patients with muscular dystrophy.In a recent report of a family with Duchenne muscular dystrophy, an affected brother with growth hormone deficiency was substantially less disabled than his younger sibs.' Based on this observation, we decided to evaluate the effect of administering a growth hormone inhibitor to nine children with Duchenne muscular dystrophy. MethodsThe nine children studied had been followed for 1 to 9 years in our Muscular Dystrophy Clinic. Their diagnosis had been confirmed by the typical clinical course, characteristic physical findings, which included pelvifemoral weakness and calf pseudohypertrophy, family history, raised serum levels of creatinine kinase (CK), lactate dehydrogenase (LDH), and serum glutamate oxaloacetate transaminase (SGOT), and abnormal findings on muscle biopsy and electromyography. The ages of these nine children at the time of entry into the study were 5, 6, 7, 7, 8, 10, 12, 12, and 14 years.After a group discussion with all the parents, and individual discussions, a written informed consent *Supported in part by a grant from the Muscular Dystrophy Association, Nassau Chapter. Received for publication 21 October 1983. Accepted for publication 17 November 1983. was obtained for each child. The study was approved by our institutional research committee (IRB).Each child received Sanorex 8 (mazindol) at a dose of 2 mg daily for 6 months. Careful manual muscle testing and peak flow during forced expiration were done for each child at the beginning of the study and at 3 and 6 months by one of us (JK), and accurate measurements of height and weight were done by at least two of us at each examination. Laboratory tests were also performed at the beginning of the study and at 3 and 6 months. Human growth hormone was assayed in serum obtained before and 90 minutes after the oral administration of clonidine (0 1 to 0 2 mg). Selenium was assayed in serum and hair by the fluorometric method.2 Glutathione peroxidase, CK, LDH, and SGOT were assayed by standard methods. Hair and serum zinc were assayed by atomic absorption spectrophotometry. Somatomedin C was assayed by radioimmunoassay. Parents were instructed in the method o...

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Hormones and liver mitochondria: Effects of growth hormone and thyroxine on respiration, fluorescence of 1-anilino-8-naphthalene sulfonate and enzyme activities of complex I and II of submitochondrial particles

Cited by 29 publications

References 26 publications

Growth Hormone Internalization in Mitochondria Decreases Respiratory Chain Activity

Growth Hormone Internalization in Mitochondria Decreases Respiratory Chain Activity

Mitochondrial Respiratory Chain Adjustment to Cellular Energy Demand

Growth hormone inhibition causes increased selenium levels in Duchenne muscular dystrophy: a possible new approach to therapy.

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