Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:Partial purification from rat liver microsomes of three native protein phosphatases with activity towards HMG-CoA reductase. 633 Feb 55

Virus-induced myositis is an emerging global affliction that remains poorly characterized with few treatment options. Moreover, muscle-tropic viruses often spread to the CNS, causing dramatically increased morbidity. Therefore, there is an urgent need to explore genetic factors involved in this class of human disease. This report investigates critical innate immune pathways affecting murine virus-induced myositis. Of particular importance, the key immune regulator src homology region 2 domain-containing phosphatase 1 (SHP-1), which normally suppresses macrophage-mediated inflammation, is a major factor in promoting clinical disease in muscle. We show that Theiler's murine encephalomyelitis virus (TMEV) infection of skeletal myofibers induces inflammation and subsequent dystrophic calcification, with loss of ambulation in wild-type (WT) mice. Surprisingly, although similar extensive myofiber infection and inflammation are observed in SHP-1(-/-) mice, these mice neither accumulate dead calcified myofibers nor lose ambulation. Macrophages were the predominant effector cells infiltrating WT and SHP-1(-/-) muscle, and an increased infiltration of immature monocytes/macrophages correlated with an absence of clinical disease in SHP-1(-/-) mice, whereas mature M1-like macrophages corresponded with increased myofiber degeneration in WT mice. Furthermore, blocking SHP-1 activation in WT macrophages blocked virus-induced myofiber degeneration, and pharmacologic ablation of macrophages inhibited muscle calcification in TMEV-infected WT animals. These data suggest that, following TMEV infection of muscle, SHP-1 promotes M1 differentiation of infiltrating macrophages, and these inflammatory macrophages are likely involved in damaging muscle fibers. These findings reveal a pathological role for SHP-1 in promoting inflammatory macrophage differentiation and myofiber damage in virus-infected skeletal muscle, thus identifying SHP-1 and M1 macrophages as essential mediators of virus-induced myopathy.
...
PMID:SHP-1-dependent macrophage differentiation exacerbates virus-induced myositis. 2568 45