In vitro effects of glucocorticoid on mitochondrial energy metabolism

Martens, Margaret E.; Peterson, Pamela E.; Lee, C.P.

doi:10.1016/s0005-2728(05)80232-4

Cited by 50 publications

(36 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In particular, reported prolactin effects on liver and white adipose tissue lipogenic gene expression and function are opposite to those observed after ghrelin treatment in the current study (1). In addition, excess glucocorticoids are not reported to exert independent effects on hepatic lipogenesis and lipid deposition (14,29,54), whereas most (16,18,30), although not all (55), reports agree on their suppressive or null effect on skeletal muscle mitochondrial function. Thus, taken together, the above observations do not support a major role of additional hypophyseal hormonal changes in observed metabolic effects.…”

Section: Discussioncontrasting

confidence: 64%

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

Barazzoni

Bosutti

Stebel

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

221

171

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 64%

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

Barazzoni

Bosutti

Stebel

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

221

171

View full text Add to dashboard Cite

show abstract

“…As this is not the case here, it suggests that oxidative phosphorylation is impaired. In support of this, a decreased ADP/O ratio has been reported, suggesting an impairment of oxidative phosphorylation, in isolated skeletal muscle mitochondria treated in vitro by GCTC [42].…”

Section: Discussionmentioning

confidence: 60%

Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats

Dumas

Biélicki²,

Renou³

et al. 2005

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis: Glucocorticoid treatments are associated with increased whole-body oxygen consumption. We hypothesised that an impairment of muscle energy metabolism can participate in this increased energy expenditure. Methods: To investigate this possibility, we have studied muscle energetics of dexamethasone-treated rats (1.5 mg kg −1 day −1 for 6 days), in vivo by 31 P NMR spectroscopy. Results were compared with control and pair-fed (PF) rats before and after overnight fasting. Results: Dexamethasone treatment resulted in decreased phosphocreatine (PCr) concentration and PCr:ATP ratio, increased ADP concentration and higher PCr to γ-ATP flux but no change in β-ATP to β-ADP flux in gastrocnemius muscle. Neither 4 days of food restriction (PF rats) nor 24 h fasting affected high-energy phosphate metabolism. In dexamethasone-treated rats, there was an increase in plasma insulin and non-esterified fatty acid concentration. Conclusions/ interpretation: We conclude that dexamethasone treatment altered resting in vivo skeletal muscle energy metabolism, by decreasing oxidative phosphorylation, producing ATP at the expense of PCr.

show abstract

“…The underlying mechanisms of these and other effects are not yet fully clear (see e.g. Hall, 1991Hall, , 1992Martens et al, 1991).Our objective here was to identify the significant subcelMar sites of action of methylprednisolone on the rate of oxygen consumption of ConA-stimulated rat thymocytes. There…”

mentioning

confidence: 99%

“…The underlying mechanisms of these and other effects are not yet fully clear (see e.g. Hall, 1991Hall, , 1992Martens et al, 1991).…”

mentioning

confidence: 99%

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin‐A‐stimulated thymocytes

Buttgereit

Grant

Müller

et al. 1994

European Journal of Biochemistry

View full text Add to dashboard Cite

The glucocorticoid methylprednisolone has clinically important anti;inflammatory effects at high concentrations through unknown mechanisms. Methylprednisolone at 0.2 mg/107 cells inhibits respiration in Concanavalin-A(ConA)-stimulated thymocytes from rats by about 20%. We have used topdown elasticity analysis to identify the blocks of reactions within oxidative phosphorylation in thymocytes whose kinetics are significantly affected by treatment with methylprednisolone. At this concentration methylprednisolone greatly inhibited the reactions of substrate oxidation and increased mitochondrial proton leak but did not significantly affect the synthesis and turnover of ATP by the phosphorylating system. Metabolic control analysis showed that oxygen consumption by ConAtreated thymocytes was controlled largely (0.51) by the phosphorylating system but also by proton leak (0.32) and substrate oxidation (0.17); this is similar to the distribution of control in hepatocytes, suggesting that this pattern may be general in cells. Methylprednisolone lowered control by the phosphorylating system to 0.26 and raised control by substrate oxidation to 0.37. From these results we conclude that the inhibition of respiration in ConA-stimulated thymocytes by methylprednisolone at this concentration results from an inhibition of substrate oxidation and a smaller stimulation of mitochondrial proton leak, with only a minor contribution of any effects within the phosphorylating system.The therapeutic effects of glucocorticoids are mostly receptor-mediated. However, clinical observations and experimental findings suggest that there are also rapid direct effects that are not mediated by induction or repression of specific genes. It is well known that the application of methylprednisolone in megadoses is an effective treatment in acute situations of autoimmune diseases (see e.g. Barile and La- Abbreviations. ConA, concanavalin A ; C, overall flux control coefficient; E , overall elasticity coefficient, J,,, or J,, total rate of oxygen consumption; J , rate of oxygen consumption required to pump protons out at a rate equal to their rate of return through the phosphorylating system ; JL, rate of oxygen consumption required to pump protons out at a rate equal to their rate of return through the proton leak; A tym, mitochondrial membrane potential; FCCP, carbonyl cyanide p-trifluoromethoxyphenylhydrazone; Ph,MeP+, triphenylmethylphosphonium cation ; Ph,MePBr, triphenylmethylphosphonium bromide ; P/O ratio, ATP molecules synthesized0 atom consumed; ADP/O ratio, ADP molecules consumed/O atom consumed. The superscripts and subscripts S, L and P refer to the three blocks of reactions that produce or consume dtyy,: substrate oxidation (cytosolic catabolic reactions, citric acid cycle, electron transport chain), proton leak (leak of protons and any proton-transporting cation cycles across the mitochondrial inner membrane) and the phosphorylation system (ATP synthesis and transport, all cellular ATP-consuming reactions) respectively. valle, 1992; de Gla...

show abstract

In vitro effects of glucocorticoid on mitochondrial energy metabolism

Cited by 50 publications

References 37 publications

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle

Dexamethasone impairs muscle energetics, studied by 31P NMR, in rats

The effects of methylprednisolone on oxidative phosphorylation in Concanavalin‐A‐stimulated thymocytes

Contact Info

Product

Resources

About