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)

Electrical stimulation of neonatal cardiac myocytes produces hypertrophy and cellular maturation with increased mitochondrial content and activity. To investigate the patterns of gene expression associated with these processes, cardiac myocytes were stimulated for varying times up to 72 hr in serum-free culture. The mRNA contents for genes associated with transcriptional activation [c-fos, c-jun, JunB, nuclear respiratory factor 1 (NRF-1)], mitochondrial proliferation [cytochrome c (Cyt c), cytochrome oxidase], and mitochondrial differentiation [carnitine palmitoyltransferase I (CPT-I) isoforms] were measured. The results establish a temporal pattern of mRNA induction beginning with c-fos (0.25-3 hr) and followed sequentially by c-jun (0.5-3 hr), JunB (0.5-6 hr), NRF-1 (1-12 hr), Cyt c (12-72 hr), and muscle-specific CPT-I (48-72 hr). Induction of the latter was accompanied by a marked decrease in the liver-specific CPT-I mRNA, thus supporting the developmental fidelity of this pattern of gene regulation. Consistent with a transcriptional mechanism, electrical stimulation increased c-fos, beta-myosin heavy chain, and Cyt c promoter activities. These increases coincided with a rise in their respective endogenous gene transcripts. NRF-1, cAMP response element, and Sp-1 site mutations within the Cyt c promoter reduced luciferase expression in both stimulated and nonstimulated myocytes. Mutations in the NRF-1 and CRE sites inhibited the induction by electrical stimulation (5-fold and 2-fold, respectively) whereas mutation of the Sp-1 site maintained or increased the fold induction. This finding is consistent with the appearance of NRF-1 and fos/jun mRNAs prior to that of Cyt c and suggests that induction of these transcription factors is a prerequisite for the transcriptional activation of Cyt c expression. These results support a regulatory role for NRF-1 and possibly AP-1 in the initiation of mitochondrial proliferation.
 ...
PMID:Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. 932 21

Current evidence suggests that ginsenosides inhibit methamphetamine (MA)-induced changes in behavior, but the precise mechanisms that underlie this effect are yet to be determined. We examined the role of adenosine receptors in the ginsenoside-induced changes in hyperlocomotion and conditioned place preference (CPP) in mice that occurred in response to administration of MA (2 mg/kg, i.p. x 1 or 2 mg/kg, i.p. x 6). Changes in circling behavior paralleled changes in CPP in the presence of MA. Pre-treatment with ginsenosides (50 or 150 mg/kg, i.p.) attenuated the MA-induced circling behavior and CPP. This attenuation was reversed by the adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chrostyryl)xanthine (CSC; 0.5 and 1.0 mg/kg) in a dose-dependent manner, but neither the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 0.5 and 1.0 mg/kg) nor the A2B receptor antagonist alloxazine (ALX; 1.5 and 3.0 mg/kg) had any such effect. MA-induced increases in activator protein (AP)-1 DNA binding activity, Fos-related antigen immunoreactivity (FRA-IR), proenkephalin mRNA expression, and proenkephalin-like immunoreactivity were reduced consistently in the striatum of animals that were pretreated with ginsenosides. These reductions were largely prevented by CSC, but not by CPT or ALX. Our results suggest that the stimulation of A2A receptors by ginsenosides attenuates the changes in behavior and the increases in AP-1 DNA binding activity, FRA-IR, and proenkephalin gene expression in mouse striatum that are induced by MA.
 ...
PMID:Ginsenosides attenuate methamphetamine-induced behavioral side effects in mice via activation of adenosine A2A receptors: possible involvements of the striatal reduction in AP-1 DNA binding activity and proenkephalin gene expression. 1568 Feb 2

Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC was induced by Fsk and select G protein-coupled receptor (GPCR) agonists, though IL-6 levels did not directly correlate with global cAMP levels. Treatment with PKA selective 6-Bnz-cAMP or Epac selective 8-CPT-2Me-cAMP cAMP analogs revealed a predominant role for PKA in cAMP-mediated induction of IL-6. IL-6 promoter mutations demonstrated that AP-1 and CRE transcription sites were required for Fsk to stimulate IL-6 expression. Our present study defines an AC2 cAMP signaling compartment that specifically regulates IL-6 expression in BSMC via Epac and PKA and demonstrates that other AC isoforms are excluded from this pool.
...
PMID:Non-raft adenylyl cyclase 2 defines a cAMP signaling compartment that selectively regulates IL-6 expression in airway smooth muscle cells: differential regulation of gene expression by AC isoforms. 2436 43