Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032290 (aspiration pneumonia)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue is the major site of estrogen formation in postmenopausal women. We have previously reported (Simpson, E.R., Ackerman, G.E., Smith, M.E. and Mendelson, C.R. (1981) Proc. Natl. Acad. Sci. (U.S.A.) 78, 5690-5694; Mendelson, C.R., Cleland, W.H., Smith, M.E. and Simpson, E.R. (1982) Endocrinology 111, 1077-1085) that aromatase activity of human adipose stromal cells in culture is stimulated by glucocorticoids and by dibutyryl cyclic AMP (Bt2-cAMP). In order to establish which physiological factors might stimulate aromatase activity of these cells by activation of adenylate cyclase, we have investigated the roles of adrenocorticotropin (ACTH) and isoproterenol to increase cyclic AMP levels and stimulate the aromatization of androstenedione. In the presence of methylisobutylxanthine (MIX), ACTH stimulated cyclic AMP formation and aromatase activity in a time- and concentration-dependent manner. The concentration of ACTH required for half-maximal stimulation was approximately 10(-8) M. Isoproterenol, in the presence of MIX, stimulated cyclic AMP formation in a time- and concentration-dependent fashion, and also stimulated aromatase activity. These effects of isoproterenol appeared to be mediated by binding of the agonist to a population of beta-adrenergic receptors. On the basis of these and our previous studies, we suggest that ACTH may play an important role in stimulating estrogen formation by human adipose tissue, both directly, and by stimulating the adrenal cortex to produce both substrate, androstenedione, and inducing agent, namely cortisol.
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PMID:Regulation of aromatase activity of cultured adipose stromal cells by catecholamines and adrenocorticotropin. 620 18

A 10-wk-old infant girl with severe hypertrophy of the septal and atrial walls by cardiac ultrasound, developed progressive ventricular wall thickening and died of aspiration pneumonia at 5 mo of age. Postmortem examination revealed ventricular hypertrophy and massive atrial wall thickening due to glycogen accumulation. A skeletal muscle biopsy showed increased free glycogen and decreased activity of phosphorylase b kinase (PHK). The report of a pathogenic mutation (R531Q) in the gene (PRKAG2) encoding the gamma2 subunit of AMP-activated protein kinase (AMPK) in three infants with congenital hypertrophic cardiomyopathy, glycogen storage, and "pseudo PHK deficiency" prompted us to screen this gene in our patient. We found a novel (R384T) heterozygous mutation in PRKAG2, affecting an arginine residue in the N-terminal AMP-binding domain. Like R531Q, this mutation reduces the binding of AMP and ATP to the isolated nucleotide-binding domains, and prevents activation of the heterotrimer by metabolic stress in intact cells. The mutation was not found in DNA from the patient's father, the only available parent, and is likely to have arisen de novo. Our studies confirm that mutations in PRKAG2 can cause fatal infantile cardiomyopathy, often associated with apparent PHK deficiency.
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PMID:Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase. 1766 62