Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the isolation of a novel human circulating proopiomelanocortin-derived peptide, VA-beta-MSH, from hemofiltrate and its pharmacological characterization. Screening for lipolytic activity in differentiated 3T3-L1 adipocytes led to the isolation from a hemofiltrate peptide library by alternating reverse phase and cation exchange chromatography. In the course of this isolation, we also identified human beta-MSH-(1-22). We synthesized VA-beta-MSH by the N-(9-fluorenyl)-methoxycarbonyl (F-moc) solid phase method and used synthetic beta-MSH-(1-22) to confirm that both isolated peptides are lipolytically active in a dose-dependent manner in differentiated 3T3-L1 adipocytes in the nanomolar range. Using cAMP ELISA, we demonstrate that stimulation with both peptides caused a strong cAMP elevation in this cell system. Furthermore, we show that the selective inhibitors of cAMP-dependent protein kinase, 8-(4-Chlorophenylthio)adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-CPT-cAMPS); N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), significantly reduce VA-beta-MSH- and beta-MSH-(1-22)-mediated lipolysis. Although isolated after its lipolytic activity on 3T3-L1 cells, this newly identified circulating human melanocortin may serve other functions in human physiology. Moreover, the fact that these peptides have been identified after a functional assay, but have been overseen in large proteomic approaches, underscores the importance of such approaches in identifying previously undescribed circulating bioactive molecules.
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PMID:Isolation and characterization of a novel proopiomelanocortin-derived peptide from hemofiltrate of chronic renal failure patients. 1565 78

In rats and humans estradiol attenuates neuroendocrine responses to hypoglycemia. Since neuroendocrine responses to hypoglycemia are mediated by hypothalamic neurons, we assessed if estradiol attenuates hypoglycemia-induced gene expression in the hypothalamus in female ovariectomized mice. As expected, estradiol-implanted ovariectomized mice exhibited increased plasma estradiol, increased uterine weight, decreased body weight, decreased visceral adiposity, and enhanced glucose tolerance with decreased plasma insulin. Estradiol-implanted mice exhibited attenuated hypoglycemia-induced gene expression of both glucose transporter 1 (Glut1) and inhibitor of kappa beta signaling (IkappaB) in the hypothalamus but not in the liver. Estradiol also attenuated hypoglycemia-induced plasma glucagon, pituitary proopiomelanocortin (POMC), and adrenal c-fos, consistent with impaired counterregulatory responses to hypoglycemia. In addition, estradiol inhibited hypothalamic expression of carnitine palmitoyltransferase (CPT1a and CPT1c) and pyruvate dehydrogenase kinase 4 (PDK4), effects that would be expected to enhance the accumulation of long-chain fatty acids and glycolysis. Taken together, these findings suggest hypothalamic mechanisms mediating attenuation of hypoglycemia-induced neuroendocrine responses.
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PMID:Estradiol impairs hypothalamic molecular responses to hypoglycemia. 1944 9

PPARalpha is a lipid-activable transcription factor that mediates the adaptive response to fasting. Recent data indicate an important role of brain PPARalpha in physiological functions. However, it has not yet been shown whether PPARalpha in brain can be activated in the fasting state. Here we demonstrate that fasting of rats increased mRNA concentrations of typical PPARalpha target genes implicated in beta-oxidation of fatty acids (acyl-CoA oxidase, carnitine palmitoyltransferase-1, medium chain acyl-CoA dehydrogenase) and ketogenesis (mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase) in pituitary gland and partially also in frontal cortex and diencephalon compared to nonfasted animals. These data strongly indicate that fasting activates PPARalpha in brain and pituitary gland. Furthermore, pituitary prolactin and luteinizing hormone-beta mRNA concentrations were increased upon fasting in wild-type mice but not in mice lacking PPARalpha. For proopiomelanocortin and thyrotropin-beta, genotype-specific differences in pituitary mRNA concentrations were observed. Thus, PPARalpha seems to be involved in transcriptional regulation of pituitary hormones.
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PMID:Fasting Upregulates PPARalpha Target Genes in Brain and Influences Pituitary Hormone Expression in a PPARalpha Dependent Manner. 2001 57