scholarly journals Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase promoter contains a CREB binding site that regulates cAMP action in Caco-2 cells

2000 ◽  
Vol 345 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Anke EGGERS ◽  
Concha CAUDEVILLA ◽  
Guillermina ASINS ◽  
Fausto G. HEGARDT ◽  
Dolors SERRA
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Camp Response Element Binding ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Mrna Levels ◽  
Camp Response Element ◽  
Response Element ◽  
Kinase A

cAMP increases transcription of the mitochondrial (mit.) gene for 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase, which encodes an enzyme that has been proposed as a control site of ketogenesis. The incubation of Caco-2 cells with cAMP increased mit.HMG-CoA synthase mRNA levels 4-fold within 24 h. We have identified an active cAMP-response element (CRE) located 546 bp upstream of the mit.HMG-CoA synthase promoter that is necessary for the induction of expression by dibutyryl cAMP. Co-transfections of constructs, containing the CRE element of the mit.HMG-CoA synthase promoter fused to the gene for chloramphenicol acetyltransferase, with protein kinase A and a dominant-negative mutant of cAMP-response-element-binding protein (CREB) show that the response to cAMP is mediated by the transcription factor CREB. The CRE element confers responsiveness of protein kinase A to a heterologous promoter in transfection assays in Caco-2 cells. Gel-retardation assays revealed that the mit.HMG-CoA synthase CRE binds to recombinant CREB. The shifted band obtained with the putative mit.HMG-CoA synthase CRE sequence and nuclear proteins from Caco-2 cells competed with CRE sequences of other genes such as somatostatin and phosphoenolpyruvate carboxykinase. We conclude that the regulation of the expression of the gene for mit.HMG-CoA synthase in Caco-2 cells by cAMP is mediated by a CRE sequence in the promoter.

trans-Resveratrol ameliorates anxiety-like behaviors and neuropathic pain in mouse model of post-traumatic stress disorder

2020 ◽  
Vol 34 (7) ◽  
pp. 726-736 ◽  
Author(s):  
Yirong Yuan ◽  
Linlin Zhen ◽  
Zhi Li ◽  
Wenhua Xu ◽  
Huilin Leng ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Stress Disorder ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Single Prolonged Stress ◽  
Element Binding Protein ◽  
Prolonged Stress ◽  
Kinase A

Background: trans-Resveratrol has been extensively investigated for its anti-inflammatory, antioxidant, and anti-psychiatric properties. However, whether it could rescue posttraumatic stress disorder-like stress-induced pain abnormality is unknown. Aim: The present study examined the effects of trans-resveratrol on anxiety-like behavior and neuropathic pain induced by single-prolonged stress, which is a classical animal model for mimicking posttraumatic stress disorder. Methods: The single-prolonged stress-induced anxiety-like behavior and pain response were detected by the novelty suppressed feeding, marble burying, locomotor activity, von Frey, and acetone-induced cold allodynia tests in mice. The serum corticosterone levels and glucocorticoid receptor, protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression were detected by enzyme-linked immunosorbent assay and immunoblot analyses. Results: trans-Resveratrol reversed single-prolonged stress-induced increased latency to feed and the number of marbles buried in the novelty suppressed feeding and marble burying tests, but did not significantly influence locomotion distance in the locomotor activity test. trans-Resveratrol also reversed single-prolonged stress-induced cold and mechanical allodynia. Moreover, single-prolonged stress induced abnormality in the limbic hypothalamus-pituitary-adrenal axis was reversed by trans-resveratrol, as evidenced by the fact that trans-resveratrol reversed the differential expression of glucocorticoid receptor in the anxiety- and pain-related regions. In addition, trans-resveratrol increased protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels, which were decreased in mice subjected to single-prolonged stress. Conclusions: These results provide compelling evidence that trans-resveratrol protects neurons against posttraumatic stress disorder-like stress insults through regulation of limbic hypothalamus-pituitary-adrenal axis function and activation of downstream neuroprotective molecules such as protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression.

Impaired cAMP-mediated gene expression and decreased cAMP response element binding protein in senescent cells

1996 ◽  
Vol 271 (1) ◽  
pp. C362-C371 ◽  
Author(s):  
J. H. Chin ◽  
M. Okazaki ◽  
J. S. Frazier ◽  
Z. W. Hu ◽  
B. B. Hoffman
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
Kinase A

The capacity of various growth factors to induce c-fos expression is diminished with senescence. Because adenosine 3',5'-cyclic monophosphate (cAMP)-mediated responses are also blunted with aging, we wondered whether cAMP-induced c-fos gene expression might be impaired with senescence. Using IMR fibroblasts, we found that prostaglandin E1 (PGE1) and forskolin, stimulators of cAMP accumulation in young and senescent cells, increased abundance of c-fos and junB mRNA more in young than senescent cells. The abundance of the cAMP response element binding protein (CREB), a transcription factor which enhances gene expression when phosphorylated by protein kinase A, was markedly decreased in both whole cell and nuclear extracts of senescent cells, in both Western blotting and in gel retardation assays. Also, PGE1-induced phosphorylation of CREB by protein kinase A was markedly attenuated in senescent cells. There is a marked decrement in expression of CREB with senescence, and the results suggest the possibility that the diminished expression of CREB may contribute to altered cAMP-mediated regulation of gene expression with senescence.

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