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)

The precise molecular events involved in growth factor-mediated cell proliferation in eukaryotes have not been entirely elucidated. Identification and characterization of the itnracellular molecular signaling systems linking growth factor function with nuclear events would provide insight into the regulatory mechanisms governing eukaryotic cell growth. In this report, we demonstrate that serum-deprived rat H4IIE hepatoma cells enter a quiescent state and remain viable in the absence of serum for up to 7 days. These cells can be stimulated to transverse the cell cycle and proliferate in response to epidermal growth factor (EGF) after a 24-h lag phase. We were able to completely mimic the mitogenic effects of EGF with 8-p-chlorophenylthio-cAMP (8-CPT-cAMP) but only partially with N6-(Bu)2-cAMP. EGF and 8-CPT-cAMP together induce a synergistic increase in H4IIE hepatoma cell proliferation. The calcium ionophore A23187 and the phorbol ester, 4 beta-phorbol 12-myristate 13-acetate had little effect on H4IIE cell proliferation. EGF treatment led to a rapid and transient increase of intracellular cAMP concentration. Both 8-CPT-cAMP and EGF were also equally effective in causing a rapid and transient induction of c-fos and c-myc protooncogene mRNA levels when added to growth-arrested H4IIE cells while A23187, N-(Bu)2-cAMP, and 4 beta-phorbol 12-myristate 13-acetate were significantly less effective. Both EGF and 8-CPT-cAMP affect protooncogene expression in growth-arrested rat H4IIE hepatoma cells primarily at the transcriptional level. Localization and semi-quantification of nuclear pp55c-fos and 63 (kilodalton)-myc protooncoproteins by immunocolloidal gold electron microscopy revealed that EGF and/or 8-CPT-cAMP treatment of quiescent H4IIE hepatoma cells led to a marked and rapid nuclear accumulation of these proteins in discrete nuclear substructures. Cummulatively, these results suggest that cAMP participates in the intracellular signaling system mediating the mitogenic and protooncogene inducing effects of EGF on growth-arrested rat H4IIE hepatoma cells.
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PMID:Epidermal growth factor induction of cellular proliferation and protooncogene expression in growth-arrested rat H4IIE hepatoma cells: role of cyclic adenosine monophosphate. 254 62

Peritoneal sepsis results in downregulation of the gene that codes for the hepatic mitochondrial enzyme carnitine palmitoyltransferase (CPT). The inhibition of hepatic CPT transcription by sepsis is thought to be mediated, in part, by increased expression of the leucine-zipper DNA transcription factor c-fos. In a cecal ligation and puncture (CLP) model, we examined the temporal effect of surgical treatment (cecal excision) on sepsis-induced inhibition of CPT gene expression. We investigated the hypothesis that Fos protein level will inversely correlate with the regulation of CPT gene expression. Specifically, we studied hepatic Fos nucleoprotein accumulation and CPT gene expression as measured by total mitochondrial CPT activity, CPT protein, and CPT mRNA. We investigated the following groups: (i) CLP followed by cecal excision 6, 12, or 24 hr following initial insult, (ii) concurrent CLP control group, and (iii) concurrent sham CLP reference group. When measured 48 hr following initial surgical insult, we conclude that: (i) in the absence of surgical treatment, peritoneal contamination results in a decrease in hepatic CPT gene expression and an increase in Fos nucleoprotein accumulation; (ii) surgical treatment at 6 or 12 hr following initial insult prevents the downregulation in hepatic CPT gene expression and does not result in Fos nucleoprotein accumulation; and (iii) surgical treatment at 24 hr following insult did not prevent the downregulation of hepatic CPT gene expression and results in an increase in hepatic Fos nucleoprotein accumulation. These data are consistent with the hypothesis that sepsis-induced regulation of hepatic c-fos gene expression, in part, is responsible for the downregulation of CPT gene expression.
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PMID:The effect of surgical treatment following peritoneal sepsis on hepatic gene expression. 859 99

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.
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PMID:Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. 932 21

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

The objective of the study was to investigate the regulatory actions of unacylated ghrelin (UAG) on glucose-sensitive (GS) neurons and glycolipid metabolism in the lateral hypothalamus area (LHA) and its involvement with orexin-A-immunopositive neurons. The effects of UAG administered into the LHA on GS neurons discharges and glycolipid metabolism were detected by single neuron discharge recording, biochemical index analysis and quantitative real-time PCR; the level of c-fos protein in orexin-A-immunopositive neurons was observed using immunofluorescence staining. UAG microinjected into the LHA activated glucose-inhibited neurons, which were partially blocked by pre-administration of anti-orexin-A antibody in the LHA. Furthermore, UAG microinjected into the LHA significantly reduced serum triglycerides (TG), total cholesterol, low-density lipoprotein cholesterol, blood glucose, insulin and hepatic TG levels, while elevated serum high-density lipoprotein cholesterol levels. UAG elevated the mRNA expression of carnitine palmitoyltransferase-1 and reduced the mRNA expression of acetyl-CoA carboxylase-1 in the liver. The above-mentioned effects of UAG were partially blocked by pre-administration of anti-orexin-A antibody. The expressions of orexin-A and c-fos were observed in the LHA. After UAG injection into the LHA, some neurons showed double labeling, and the percentage of double-labeled orexin-A/c-fos neurons in orexin-A-immunopositive neurons increased significantly. UAG in the LHA regulates glycolipid metabolism by activating orexin-A-immunopositive neurons in the LHA.
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PMID:Unacylated Ghrelin Regulates Glucose-Sensitive Neurons Activity and Glycolipid Metabolism via Orexin-A Neurons in the Lateral Hypothalamic Area. 3273 Dec 63