Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most of the increased protein degradation in muscle atrophy caused by starvation and denervation is due to activation of a non-lysosomal ATP-dependent proteolytic process. To determine whether expression of the ubiquitin-proteasome-dependent pathway is activated in atrophying muscles, we measured the levels of mRNA for ubiquitin (Ub) and proteasome subunits, and Ub content. After rats had been deprived of food for 1 or 2 days, the concentration of the two polyubiquitin (polyUb) transcripts increased 2-4-fold in the pale extensor digitorum longus muscle and 1-2.5-fold in the red soleus, whereas total muscle RNA and total mRNA content fell by 50%. After denervation of the soleus, there was a progressive 2-3-fold increase in polyUb mRNA for 1-3 days, whereas total RNA content fell. On starvation or denervation, Ub concentration in the muscles also rose by 60-90%. During starvation, polyUb mRNA levels also increased in heart, but not in liver, kidney, spleen, fat, brain or testes. Although the polyUb gene is a heat-shock gene that is induced in muscles under certain stressful conditions, the muscles of starving rats or after denervation did not express other heat-shock genes. On starvation or denervation, mRNA for several proteasome subunits (C-1, C-3, C-5, C-8 and C-9) also increased 2-4-fold in the atrophying muscles. When the food-deprived animals were re-fed, levels of Ub and proteasome mRNA in their muscles returned to control values within 1 day. In contrast, no change occurred in the levels of muscle mRNAs encoding cathepsin L, cathepsin D and calpain 1 on denervation or food deprivation. Thus polyUb and proteasome mRNAs increased in atrophying muscles in co-ordination with activation of the ATP-dependent proteolytic process.
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PMID:Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy. 774 90

Insulin-like growth factor I (IGF-I) and growth hormone (GH) exert their anabolic actions by increasing protein synthesis, but only IGF-I has been reported to impede protein breakdown. Using a model of myofibrillar catabolism produced by dexamethasone (Dex) we have reported that IGF-I down-regulates Dex-induced mRNAs for Ubiquitin (Ub) and Ub-conjugating enzymes (E2) in skeletal muscle, whereas GH had no significant effect. In the present study, we used the same model to determine whether IGF-I (0.35 mg/100 g BW) and/or GH (0.3 mg/100 g BW) have effects on proteasome subunit mRNAs in skeletal muscles of rats treated with Dex (0.5 mg/100 g BW) for 3 days. Dex caused significant increases in C-2, -3, and -8 proteasome subunit mRNAs (6.0-, 4.0-, and 6.6-fold increases, respectively). Injections of IGF-I in Dex-treated animals caused significant suppression of transcripts for C-2, -3, and -8 (32%, 42%, and 40%, respectively). GH restored the serum IGF-I levels in Dex treated animals, but caused further increases in proteasome subunit mRNAs (C-2, 35%; C-3, 34.5%; C-8, 33%; C-6, 42%; C-5, 32%; C-9, 37%). Administration of IGF-I in the Dex/GH-treated animals decreased the mRNAs of proteasome subunits in a manner and degree similar to those observed in the Dex/IGF-I group. Surprisingly, injection of GH alone in normal animals increased proteasome subunit mRNAs in skeletal muscle (C-2, 85%; C-3, 109%; C-8, 91%). This effect of GH on proteasome subunit mRNAs was also observed in liver. These findings suggest, therefore, that suppression of Dex-induced expression of proteasome subunit mRNAs in skeletal muscle is one of the mechanisms by which IGF-I exerts its antiproteolytic activity in catabolic states. On the other hand, the biological function of GH in regulating proteasome subunits needs further investigation.
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PMID:Divergent regulation of proteasomes by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone. 1242 29