Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical observations suggest that overt rhabdomyolysis may occur if severe hypophosphatemia is superimposed upon a pre-existing subclinical myopathy. To examine this possibility, a subclinical muscle cell injury was induced in 23 dogs by feeding them a phosphorus- and calorie-deficient diet until they lost 30% of their original weight. To induce acute, severe hypophosphatemia in the animals after partial starvation, 17 of the dogs were given large quantities of the same phosphorus-deficient diet in conjunction with an oral carbohydrate supplement, which together provided 140 kcal/kg per day. After phosphorus and caloric deprivation, serum phosphorus and creatine phosphokinase (CPK) activity were normal. Total muscle phosphorus content fell from 28.0+/-1.3 to 26.1+/-2.5 mmol/dg fat-free dry solids. Sodium, chloride, and water contents rose. These changes resembled those observed in patients with subclinical alcoholic myopathy. When studied after 3 days of hyperalimentation, the animals not receiving phosphorus showed weakness, tremulousness, and in some cases, seizures. Serum phosphorus fell, the average lowest value was 0.8 mg/dl (P <0.001). CPK activity rose from 66+/-357 to 695+/-1,288 IU/liter (P <0.001). Muscle phosphorus content fell further to 21.1+/-7.7 mmol/dg fat-free dry solids (P <0.001). Muscle Na and Cl contents became higher (P <0.01). Sections of gracilis muscle showed frank rhabdomyolysis.6 of the 23 phosphorus- and calorie-deprived dogs were also given 140 kal/kg per day but in addition, each received 147 mmol of elemental phosphorus. These dogs consumed their diet avidly and displayed no symptoms. They did not become hypophosphatemic, their CPK remained normal, and derangements of cellular Na, Cl, and H(2)O were rapidly corrected. The gracilis muscle appeared normal histologically in these animals. These data suggest that a subclinical myopathy may set the stage for rhabdomyolysis if acute, severe hypophosphatemia is superimposed. Neither acute hypophosphatemia nor rhabdomyolysis occur if abundant phosphorus is provided during hyperalimentation.
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PMID:Hypophosphatemia and rhabdomyolysis. 74 77

Strenuous prolonged running causes muscle fibre necrosis in skeletal muscles. The muscle injury is associated with inflammation and a strong increase in the total activities of certain acid hydrolases a few days after exertion. The activity changes of acid hydrolases quantitatively well reflect the severity of histopathological changes during the myopathy (for review see Salminen, Acta Physiol Scand [Suppl 539] 1985). In this study male NMRI-mice were exposed to a protocol of fasting and refeeding together with or without a 6 h run on a treadmill at 13.5 m.min-1. The animals were killed 4 days after the exercise and samples from the red part of quadriceps femoris were analyzed for arylsulfatase (ASase) and beta-glucuronidase (GUase) activities. Starvation protocols did not affect ASase or GUase. Running caused a 3.2-fold increase in ASase and a 5.1-fold increase in GUase. If mice were exercised in the fasted condition a normal exercise response occurred in both activities, but when mice were exercised 2 days after the finish of fasting the exercise response was greatly diminished. Thus food deprivation followed by 2 days refeeding induces a protection against exercise myopathy in mice. The protection greatly resembles that induced by regular endurance training preceding strenuous prolonged exertion.
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PMID:Food deprivation decreases the exertion-induced acid hydrolase response in mouse skeletal muscle. 334 83

Effect of starvation or ACTH injection on the urinary level and profile of L-carnitine and its derivatives was studied in four healthy adult men or in a normal child and two patients with myopathy, respectively. Mean total L-carnitine level in the control urine sample obtained before starvation was 389 +/- 34 mumol . man . day. The percentage distribution was found to be 46% for free-, 9% for acetyl- and 45% for acyl-L-carnitine. The acyl-L-carnitine fraction contained short-chain (65%) and long-chain acyl-L-carnitine (35%). With 2-day starvation urinary excretion of free-L-carnitine was slightly decreased and, in contrast, that of acetyl-L-carnitine was considerably increased, resulting in a significant increase in urinary total L-carnitine levels. Urinary excretion of acyl-L-carnitine was increased two-folds with starvation, but that of long-chain acyl-L-carnitine was not changed. In a normal child (female, 3.5 yr) and two patients (female, 4.5 yr and male, 23 yr) with myopathy, ACTH injection induced a significant elevation of urinary total L-carnitine levels, being mainly caused by an increased excretion of free-L-carnitine and, in the adult patient, acyl-L-carnitine. Muscle total L-carnitine contents were normal in two children but abnormally low in the adult patient, who had simultaneously very low urinary total L-carnitine level before ACTH injection. Thus, in the adult patient myopathy might be possibly caused in part by carnitine deficiency. Starvation and ACTH-induced changes in urinary level and profile of L-carnitine and its derivatives were discussed in relation to carnitine biosynthesis as well as renal regulation of carnitine clearance.
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PMID:Urinary profile of L-carnitine and its derivatives in starved normal persons and ACTH injected patients with myopathy. 631 1

We studied a 23-year-old man with lipid storage myopathy. Five members of his family had hyperlipoproteinemia, and his consanguineous parents had elevated serum creatine kinase levels, although only the father showed clinical evidence of myopathy. The patient's intramuscular carnitine content was slightly reduced, but the reduction was not significant compared with the average value for reported cases with carnitine deficiency. Urinary excretion of carnitine showed good responses to starvation, long-chain fatty acid loading, and corticotropin administration. Therefore, his carnitine metabolism was normal. Administration of corticotropin or carnitine did not bring about any improvement of the symptoms. A connection between lipid storage myopathy and hyperlipoproteinemia was suggested.
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PMID:Lipid storage myopathy in familial hyperlipoproteinemia. 672 23

Skeletal muscle atrophy is a common feature in alcoholism that affects up to two-thirds of alcohol misusers, and women appear to be particularly susceptible. There is also some evidence to suggest that malnutrition exacerbates the effects of alcohol on muscle. However, the mechanisms responsible for the myopathy remain elusive, and some studies suggest that acetaldehyde, rather than alcohol, is the principal pathogenic perturbant. Previous reports on rats dosed acutely with ethanol (<24 h) have suggested that increased proto-oncogene expression (i.e., c-myc) may be a causative process, possibly via activating preapoptotic or transcriptional pathways. We hypothesized that 1) increases in c-myc mRNA levels also occur in muscle exposed chronically to alcohol, 2) muscle of female rats is more sensitive than that from male rats, 3) raising acetaldehyde will also increase c-myc, 4) prior starvation will cause further increases in c-myc mRNA expression in response to ethanol, and 5) other genes involved in apoptosis (i.e., p53 and Bcl-2) would also be affected by alcohol. To test this, we measured c-myc mRNA levels in skeletal muscle of rats dosed either chronically (6-7 wk; ethanol as 35% of total dietary energy) or acutely (2.5 h; ethanol as 75 mmol/kg body wt ip) with ethanol. All experiments were carried out in male Wistar rats (approximately 0.1-0.15 kg body wt) except the study that examined gender susceptibility in male and female rats. At the end of the studies, rats were killed, and c-myc, p53, and Bcl-2 mRNA was analyzed in skeletal muscle by RT-PCR with an endogenous internal standard, GAPDH. The results showed that 1) in male rats fed ethanol chronically, there were no increases in c-myc mRNA; 2) increases, however, occurred in c-myc mRNA in muscle from female rats fed ethanol chronically; 3) raising endogenous acetaldehyde with cyanamide increased c-myc mRNA in acute studies; 4) starvation per se increased c-myc mRNA levels and at 1 day potentiated the acute effects of ethanol, indicative of a sensitization response; 5) the only effect seen with p53 mRNA levels was a decrease in muscle of rats starved for 1 day compared with fed rats, and there was no statistically significant effect on Bcl-2 mRNA in any of the experimental conditions. The increases in c-myc may well represent a preapoptotic effect, or even a nonspecific cellular stress response to alcohol and/or acetaldehyde. These data are important in our understanding of a common muscle pathology induced by alcohol.
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PMID:Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression. 1287 71

Heart failure (HF) is a syndrome resulting from the inability of the cardiac pump to meet the energy requirements of the body. Despite intensive work, the pathogenesis of the cardiac intracellular abnormalities that result from HF remains incompletely understood. Factors that lead to abnormal contraction and relaxation in the failing heart include metabolic pathway abnormalities that result in decreased energy production, energy transfer and energy utilization. Heart failure also affects the periphery. Patients suffering from heart failure always complain of early muscular fatigue and exercise intolerance. This is linked in part to intrinsic alterations of skeletal muscle, among which decreases in the mitochondrial ATP production and in the transfer of energy through the phosphotransfer kinases play an important role. Alterations in energy metabolism that affect both cardiac and skeletal muscles argue for a generalized metabolic myopathy in heart failure. Recent evidence shows that decreased expression of mitochondrial transcription factors and mitochondrial proteins are involved in mechanisms causing the energy starvation in heart failure. This review will focus on energy metabolism alterations in long-term chronic heart failure with only a few references to compensated hypertrophy when necessary. It will briefly describe the energy metabolism of normal heart and skeletal muscles and their alterations in chronic heart failure. It is beyond the scope of this review to address the metabolic switches occurring in compensated hypertrophy; readers could refer to well-documented reviews on this subject.
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PMID:Energy metabolism in heart failure. 1466 Jul 9

Alcoholic myopathy is a common pathology characterized by wasting due to reduced protein synthesis, although the mechanisms involved remain unclear. Women are particularly sensitive and malnutrition exacerbates the myopathy. This study aimed to address (i) whether long-term alcohol feeding alters expression of heat shock proteins (HSPs) in male and female rats; (ii) the effect of immediate alcohol dosing with or without raised levels of endogenous acetaldehyde; and (iii) the effect of starvation. To address this, (i) male and female rats were fed alcohol in the long-term (6-7 weeks as 35% of energy in a liquid diet) and compared to controls fed the same diet with isoenergetic glucose; (ii) male rats given an immediate bolus (75 mmol ethanol per kilogram body weight intraperitoneally) 2.5 hours before sacrifice and compared to controls given a dose of saline (with or without pretreatment with cyanamide-an acetaldehyde dehydrogenase inhibitor which raises endogenous acetaldehyde); (iii) male rats starved for 1 or 2 days then immediately dosed with alcohol. Protein levels of HSP 27, HSP 60, and HSP 70 were measured in muscles of male rats fed alcohol and pair-fed control rats by SDS-PAGE and Western blotting in study I. Levels of HSP 27, HSP 60, HSP 70, and HSP 90 mRNA were analyzed in hind limb skeletal muscle by reverse transcription-polymerase chain reaction with an endogenous internal standard, glyceraldehyde-3-phosphate-dehydrogenase. (i) Long-term alcohol dosage reduced HSP 27 in male rats but not in females, whereas HSP 90 mRNA increased in long-term alcohol-fed female rats but not in male rats. These changes were reflected by a similar trend in HSP protein content, although statistical significance was not achieved. (ii) There was no effect on any of the HSP mRNAs in rats dosed immediately with alcohol or in combination with cyanamide. (iii) Starvation per se for 2 days was associated with an increase in HSP 27 mRNA. Alcohol administration after 2 days starvation caused a blunting of the increased HSP 27 mRNA in starvation alone. This suggests that long-term alcohol exposure affects HSP gene expression and that this effect is moderated by sex and starvation. This may contribute to, or reflect, the biochemical lesion in alcoholic myopathy.
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PMID:Alcohol alters skeletal muscle heat shock protein gene expression in rats: these effects are moderated by sex, raised endogenous acetaldehyde, and starvation. 1678 54

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the commonest disorder of fatty acid metabolism, with a high incidence of morbidity and mortality at presentation. We report a 16 year old girl with first presentation of MCAD deficiency following an alcoholic binge and subsequent period of starvation. Presentation was as acute encephalopathy progressing to coma. Renal, cardiac and hepatic failures were managed with intensive supportive care including mechanical ventilation, inotropic support, blood products and renal replacement therapy. Diagnosis of MCAD deficiency was confirmed on day 6. The patient was discharged from hospital on day 20 with a mild proximal myopathy, which subsequently resolved. The diagnosis of MCAD deficiency requires a high index of suspicion at all ages. Precipitating factors in later life may include alcohol.
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PMID:Late presentation of medium-chain acyl-CoA dehydrogenase deficiency. 1714 76

VCP (VCP/p97) is a ubiquitously expressed member of the AAA(+)-ATPase family of chaperone-like proteins that regulates numerous cellular processes including chromatin decondensation, homotypic membrane fusion and ubiquitin-dependent protein degradation by the proteasome. Mutations in VCP cause a multisystem degenerative disease consisting of inclusion body myopathy, Paget disease of bone, and frontotemporal dementia (IBMPFD). Here we show that VCP is essential for autophagosome maturation. We generated cells stably expressing dual-tagged LC3 (mCherry-EGFP-LC3) which permit monitoring of autophagosome maturation. We determined that VCP deficiency by RNAi-mediated knockdown or overexpression of dominant-negative VCP results in significant accumulation of immature autophagic vesicles, some of which are abnormally large, acidified and exhibit cathepsin B activity. Furthermore, expression of disease-associated VCP mutants (R155H and A232E) also causes this autophagy defect. VCP was found to be essential to autophagosome maturation under basal conditions and in cells challenged by proteasome inhibition, but not in cells challenged by starvation, suggesting that VCP might be selectively required for autophagic degradation of ubiquitinated substrates. Indeed, a high percentage of the accumulated autophagic vesicles contain ubiquitin-positive contents, a feature that is not observed in autophagic vesicles that accumulate following starvation or treatment with Bafilomycin A. Finally, we show accumulation of numerous, large LAMP-1 and LAMP-2-positive vacuoles and accumulation of LC3-II in myoblasts derived from patients with IBMPFD. We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis.
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PMID:VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. 2010 22

Autophagy is a self-eating system conserved among eukaryotes, in which cellular components including organelles are entrapped into a double membrane structure called the autophagosome and then degraded by lysosomal hydrolases. In addition to its role in supplying amino acids in response to nutrient starvation, autophagy is involved in quality control to maintain cell health. Thus, inactivation of autophagy causes the formation of cytoplasmic protein inclusions, which comprise misfolded proteins and the accumulation of many degenerated organelles, resulting in liver injury, diabetes, myopathy and neurodegeneration. Furthermore, although autophagy has been considered nonselective, increasing evidence points to the selectivity of autophagy in sorting vacuolar enzymes and removal of aggregate-prone proteins and unwanted organelles. Such selectivity allows diverse cellular regulation, similar to the ubiquitin proteasome pathway. In this review, we discuss the physiological roles of selective autophagy and their molecular mechanisms.
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PMID:Selective autophagy regulates various cellular functions. 2067 Feb 74


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