Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate the cellular response of the diaphragm, extensor digitorum longus (EDL), and soleus (Sol) muscles to clinically relevant doses of cyclosporine administered to male rats over 4 wk. Control rats were provided with vehicle only. Muscle fiber types, cross-sectional areas, indexes of capillarity, and succinate dehydrogenase (SDH) activity were determined by quantitative histochemistry. Myosin heavy chain isoforms were identified by SDS-PAGE, and their proportions were measured by scanning densitometry. Serum cyclosporine level, 20-24 h after the last dose of cyclosporine, was 145 +/- 81 ng/ml. Final body weight and muscle mass were similar between the cyclosporine and control groups. In the diaphragm, EDL, and Sol, no differences were observed between the groups with regard to fiber type proportions, fiber cross-sectional areas, and proportions of myosin heavy chain isoforms. In the EDL, reductions, both in SDH activity in type I, IIx, and IIb fibers (-26 to -37%) and in indexes of capillarity (-18 to -37%), were noted. In the Sol, SDH activity and capillarity were similar between the groups. In the diaphragm of cyclosporine-treated rats, there was significant reduction in the number of capillaries around individual fibers (-5%), whereas levels of SDH activity tended to be lower. This suggests that activation history may in part determine muscle-specific responses to cyclosporine. We speculate that reduced oxidative activity and capillarity of some limb muscles contribute to reduced exercise capacity and the "deconditioned state" observed in patients receiving cyclosporine after successful solid-organ transplantation.
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PMID:Cellular adaptations of skeletal muscles to cyclosporine. 960 91

The scalene has been reported to be an accessory inspiratory muscle in the hamster. We hypothesize that with the chronic loads and/or dynamic hyperinflation associated with emphysema (Emp), the scalene will be actively recruited, resulting in functional, cellular, and biochemical adaptations. Emp was induced in adult hamsters. Inspiratory electromyogram (EMG) activity was recorded from the medial scalene and costal diaphragm. Isometric contractile and fatigue properties were evaluated in vitro. Muscle fibers were classified histochemically and immunohistochemically. Individual fiber cross-sectional areas (CSA) and succinate dehydrogenase (SDH) activities were determined quantitatively. Myosin heavy chain (MHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. All Emp animals exhibited spontaneous scalene inspiratory EMG activity during quiet breathing, whereas the scalene muscles of controls (Ctl) were silent. There were no differences in contractile and fatigue properties of the scalene between Ctl and Emp. In Emp, the relative amount of MHC(2A) was 15% higher whereas that of MHC(2X) was 14% lower compared with Ctl. Similarly, the proportion of type IIa fibers increased significantly in Emp animals with a concomitant decrease in IIx fibers. CSA of type IIx fibers were significantly smaller in Emp compared with Ctl. SDH activities of all fiber types were significantly increased by 53 to 63% in Emp. We conclude that with Emp the actively recruited scalene exhibits primary-like inspiratory activity in the hamster. Adaptations of the scalene with Emp likely relate both to increased loads and to factors intrinsic to muscle architecture and chest mechanics.
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PMID:Functional, cellular, and biochemical adaptations to elastase-induced emphysema in hamster medial scalene. 1074 27

The impact of a targeted disruption of the Igf1 gene, encoding the insulin-like growth factor I (IGF-I), on diaphragm (DIA) cellularity was studied in 2-mo-old homozygous mutant [IGF-I(-/-)] mice and their wild-type [WT; i.e., IGF-I(+/+)] littermates. DIA fiber types were classified histochemically. DIA fiber cross-sectional areas (CSA) were determined from digitized muscle sections, and fiber succinate dehydrogenase (SDH) activity was determined histochemically using a microdensitometric procedure. An acidic ATPase reaction was used to visualize capillaries. Myosin heavy chain (MyHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. The body weight of IGF-I(-/-) animals was 32% that of WT littermates. DIA fiber type proportions were unchanged between the groups. The CSAs of types I, IIa, and IIx DIA fibers of IGF-I(-/-) mutants were 63, 68, and 65%, respectively, those of WT animals (P < 0.001). The DIA thickness and the number of fibers spanning its entire thickness were reduced by 36 and 25%, respectively, in IGF-I(-/-) mice (P < 0. 001). SDH activity was significantly increased in all three types of DIA fibers of IGF-I(-/-) mutants (P < 0.05). The number of capillaries per fiber was reduced approximately 30% in IGF-I(-/-) animals, whereas the capillary density was preserved. The proportions of MyHC isoforms were similar between the groups. Muscle hypoplasia likely reflects the importance of IGF-I on cell proliferation, differentiation, and apoptosis (alone or in combination) during development, although reduced cell size highlights the importance of IGF-I on rate and/or maintenance of DIA fiber growth in the postnatal state. Reduced capillarity may result from both direct and indirect influences on angiogenesis. Improved oxidative capacity likely reflects DIA compensatory mechanisms in IGF-I(-/-) mutants.
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PMID:Influences of IGF-I gene disruption on the cellular profile of the diaphragm. 1075 Dec 6