Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A procedure for the isolation and partial purification of three hydroxymethylglutaryl coenzyme A reductase phosphatases in their native high molecular weight form from rat liver microsomes is described for the first time. Reductase phosphatase Ex (Mr 90,000), IM (Mr 75,000), and IIM (Mr 180,000) were purified 132-, 55-, and 98-fold, respectively. Treatment with 80% ethanol irreversibly inactivated the three enzymes contrary to what is found for cytosolic reductase phosphatases. The three microsomal reductase phosphatases differ among themselves and with respect to the cytosolic reductase phosphatases in molecular weight, response to inhibitors, thermal stability, and optimum pH. Indirect evidence that these three proteins are phosphatases includes their inhibition by inhibitors of phosphatase activity, such as KF, Pi, and PPi. Direct evidence includes their ability to release 32P from highly radioactive homogeneous 32P-labeled HMG-CoA reductase, this dephosphorylation being concomitant with activation of HMG-CoA reductase. The three phosphatases dephosphorylate 32P-labeled phosphorylase a, but only reductase phosphatase IIM shows glycogen synthase phosphatase activity.
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PMID:Partial purification from rat liver microsomes of three native protein phosphatases with activity towards HMG-CoA reductase. 633 Feb 55

Medications inhibiting 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase are commonly used as lipid-lowering therapy. Myopathy has been reported as a rare adverse effect in up to 0.2% of patients; however, this complication appears to be more common in patients who are concurrently receiving cyclosporin A(CsA). We present a case of a 74-year-old woman tolerating a stable dose of simvastatin 80 mg daily for hyperlipidemia. After the addition of CsA for a corneal stem limbal cell transplant, the patient experienced a cholesterol-lowering agent myopathy syndrome (CLAMS), with creatine phosphokinase values up to 78,472 U/L. We explore the interaction between simvastatin and CsA, including effects on hepatic microsomal metabolism via the cytochrome P-450 pathway, cholestasis, and myoblast histology, with a review of previous literature regarding HMG-CoA reductase inhibitors (HMGRIs) and rhabdomyolysis. Caution should be exercised in patients receiving concomitant simvastatin and CsA, and a reduced dose of simvastatin is suggested. Inhibition of HMG-CoA reductase is an accepted therapy for hyperlipidemias. The development of a CLAMS is a known potential adverse effect (1), with an increased incidence during coadministration of lovastatin and CsA, first reported by Norman et al. and East et al. in 1988 (2, 3). The interaction between the HMGRIs and CsA, which leads to this muscle toxicity, appears to be related to altered clearance of the HMGRIs with resultant increased tissue exposure (4). The majority of experience with rhabdomyolysis has been in cardiac and renal transplant patients requiring lovastatin and CsA. Theoretically, however, any of the HMGRIs may predispose a patient requiring CsA to develop myositis. In particular, there is a suggestion of an increased sensitivity of myoblasts to both lovastatin and simvastatin (5). We present a case of rhabdomyolysis in a corneal stem cell transplant patient receiving simvastatin and CsA, with a review of the literature.
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PMID:Rhabdomyolysis in a patient taking simvastatin after addition of cyclosporine therapy. 1907 94