Dataset Information

Androgens regulate mitochondrial cytochrome c oxidase and lysosomal hydrolases in mouse skeletal muscle.

ABSTRACT: The gastrocnemius, a fast-twitch white muscle, and the soleus, a slow-twitch red muscle, were studied in A/J mice. The specific activities of the lysosomal hydrolases, beta-D-glucuronidase, hexosaminidase, beta-D-galactosidase and arylsulphatase, the inner-mitochondrial-membrane enzyme cytochrome c oxidase, and the outer-mitochondrial-membrane enzyme monoamine oxidase, were greater in the soleus than in the gastrocnemius. The specific activities of the lysosomal hydrolases and cytochrome c oxidase in the gastrocnemius and soleus were substantially higher in male mice than in female mice. Orchiectomy abolished this sex difference. Testosterone increased the activities of the lysosomal hydrolases and cytochrome c oxidase and coincidentally induced muscle hypertrophy and an accretion of protein and RNA, but total DNA remained constant. Monoamine oxidase was unaffected by sex, orchiectomy and testosterone. These findings indicate that endogenous androgens regulate the activity of enzymes associated with lysosomes and the inner mitochondrial membrane, as well as muscle fibre growth in mouse skeletal muscle.

SUBMITTER: Koenig H

PROVIDER: S-EPMC1162340 | biostudies-other | 1980 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundNicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the mitochondrial electron transport chain are the primary sources of reactive oxygen species (ROS). Previous studies have shown that severe heat exposure damages mitochondria and causes excessive mitochondrial ROS production that contributes to the pathogenesis of heat-related illnesses.ObjectivesWe tested whether the antioxidant curcumin could protect against heat-induced mitochondrial dysfunction and skeletal muscle injury, and characterized the possible mechanism.MethodsMouse C2C12 myoblasts and rat flexor digitorum brevis (FDB) myofibers were treated with 5 μM curcumin; adult male C57BL/6J mice received daily curcumin (15, 50, or 100 mg/kg body weight) by gavage for 10 consecutive days. We compared ROS levels and mitochondrial morphology and function between treatment and nontreatment groups under unheated or heat conditions, and investigated the upstream mechanism and the downstream effect of curcumin-regulated ROS production.ResultsIn C2C12 myoblasts, curcumin prevented heat-induced mitochondrial fragmentation, ROS overproduction, and apoptosis (all P < 0.05). Curcumin treatment for 2 and 4 h at 37°C induced increases in ROS levels by 42% and 59% (dihydroethidium-derived fluorescence), accompanied by increases in NADPH oxidase protein expression by 24% and 32%, respectively (all P < 0.01). In curcumin-treated cells, chemical inhibition and genetic knockdown of NADPH oxidase restored ROS to levels similar to those of controls, indicating NADPH oxidase mediates curcumin-stimulated ROS production. Moreover, curcumin induced ROS-dependent shifting of the mitochondrial fission-fusion balance toward fusion, and increases in mitochondrial mass by 143% and membrane potential by 30% (both P < 0.01). In rat FDB myofibers and mouse gastrocnemius muscles, curcumin preserved mitochondrial morphology and function during heat stress, and prevented heat-induced mitochondrial ROS overproduction and tissue injury (all P < 0.05).ConclusionsCurcumin regulates ROS hormesis favoring mitochondrial fusion/elongation, biogenesis, and improved function in rodent skeletal muscle. Curcumin may be an effective therapeutic target for heat-related illness and other mitochondrial diseases.

Project description:BackgroundSirtuins are NAD+ dependent deacetylases, which regulate mitochondrial energy metabolism as well as cellular response to stress. The NAD/NADH-system plays a crucial role in oxidative phosphorylation linking sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able to directly deacetylate and activate different complexes of the respiratory chain. This prompted us to analyse sirtuin levels in skin fibroblasts from patients with cytochrome c-oxidase (COX) deficiency and to test the impact of different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate sirtuins and possibly respiratory chain enzymes in patient cells in vitro.MethodsWe assayed intracellular levels of sirtuin 1 and the mitochondrial sirtuins SIRT3 and SIRT4 in human fibroblasts from patients with COX- deficiency. Furthermore, sirtuins were measured after inhibiting complex IV in healthy control fibroblasts by cyanide and after incubation with activators SRT1720 and paeonol. To determine the effect of sirtuin inhibition at the cellular level we measured total cellular acetylation (control and patient cells, with and without treatment) by Western blot.ResultsWe observed a significant decrease in cellular levels of all three sirtuins at the activity, protein and transcriptional level (by 15% to 50%) in COX-deficient cells. Additionally, the intracellular concentration of NAD+ was reduced in patient cells. We mimicked the biochemical phenotype of COX- deficiency by incubating healthy fibroblasts with cyanide and observed reduced sirtuin levels. A pharmacological activation of sirtuins resulted in normalized sirtuin levels in patient cells. Hyper acetylation was also reversible after treatment with sirtuin activators. Pharmacological modulation of sirtuins resulted in altered respiratory chain complex activities.ConclusionsWe found inhibition of situins 1, 3 and 4 at activity, protein and transcriptional levels in fibroblasts from patient with COX-deficiency. Pharmacological activators were able to restore reduced sirtuin levels and thereby modulate respiratory chain activities.

Dataset Information

Androgens regulate mitochondrial cytochrome c oxidase and lysosomal hydrolases in mouse skeletal muscle.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets