Fetal malnutrition is associated with impairment of endogenous melatonin synthesis in pineal via hypermethylation of promoters of protein kinase C alpha and cAMP response element‐binding

2021 ◽  
Author(s):  
Tianshu Han ◽  
Wenbo Jiang ◽  
Huanyu Wu ◽  
Wei Wei ◽  
Jiang Lu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Melatonin Synthesis ◽  
Kinase C ◽  
Protein Kinase C Alpha ◽  
Fetal Malnutrition ◽  
Endogenous Melatonin

scholarly journals A novel pathway for adrenergic stimulation of cAMP-response-element-binding protein (CREB) phosphorylation: mediation via α1-adrenoceptors and protein kinase C activation

2002 ◽  
Vol 364 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Håkan THONBERG ◽  
J. Magnus FREDRIKSSON ◽  
Jan NEDERGAARD ◽  
Barbara CANNON
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Creb Phosphorylation ◽  
Kinase C ◽  
Adrenergic Antagonist ◽  
Element Binding Protein ◽  
Protein Kinase C Activation

Because of the central role of adrenergic mechanisms in the expression of crucial genes during brown adipocyte differentiation, we examined the activation (phosphorylation) of CREB (cAMP-response-element-binding protein) in mouse brown adipocytes in primary culture. We found that noradrenaline (‘norepinephrine’) stimulated CREB phosphorylation rapidly (maximum effect in ≤ 5min with slow decay) and efficiently (EC50, 6nM). The increase in CREB phosphorylation coincided with increased expression of an artificial cAMP-response-element-containing reporter construct. CREB phosphorylation was partly inhibitable, both by the β-adrenergic antagonist propranolol and by the α1-adrenergic antagonist prazosin. Adenylate cyclase hyperactivation (by forskolin) could stimulate CREB phosphorylation to the same extent as noradrenaline. The α1-adrenergic agonist cirazoline also increased CREB phosphorylation. An increase in intracellular [Ca2+] had, however, no effect, but protein kinase C activation by PMA was a potent stimulator. The cirazoline-stimulated (α1-adrenergic) CREB phosphorylation was inhibited by a desensitizing pretreatment with PMA, demonstrating that the α1-stimulation was mediated via protein kinase C activation; neither Src nor extracellular-signal-regulated kinases 1 and 2 activation was involved in the signalling process. We conclude that CREB phosphorylation in brown adipocytes is mediated not only through the classical β-adrenergic/cAMP pathway but also through a novel α1-adrenergic/protein kinase C/CREB pathway, which has not been described previously in any tissue.

Abstract 119: The Scaffolding Protein Enh1 is Essential for the Protein Kinase C or Protein Kinase D-dependent Activation of the Transcription Factor Camp-response Element Binding Protein in Cardiomyocytes

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jumpei Ito ◽  
Andrés D. Maturana
Keyword(s):  
Transcription Factor ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Splice Variants ◽  
Camp Response Element Binding ◽  
Scaffolding Protein ◽  
Camp Response Element ◽  
Lim Domains ◽  
Kinase C ◽  
Element Binding Protein

PDZ-LIM proteins form a family of the scaffolding protein essential for both embryonic and post-natal development. ENH1 (PDLIM5) is a PDZ-LIM protein, composed of an N-terminal PDZ domain and 3 LIM domains at the C-terminal end. The enh gene encodes for several splice variants that have opposite functions. ENH1 promotes the cardiomyocytes hypertrophy whereas ENH splice variants lacking LIM domains prevents it. At the molecular level, ENH1 interacts with Protein kinase C (PKC) and Protein Kinase D1 (PKD1) both kinases playing a pivotal role in the pathological remodeling of the heart. In addition, the binding of ENH1’s LIM domains to PKC is sufficient to activate the kinase without any stimulation. However, the downstream events of the ENH1-PKC/PKD1 complex remain unknown. PKC and PKD1 are known to phosphorylate the transcription factor cAMP-response element binding protein (CREB) in cardiomyocytes. We therefore hypothesized that ENH1 could be a play a role in the PKC/PKD1-dependent activation of CREB. We first found that ENH1 expression is necessary to induce the phosphorylation of CREB at Ser133 in neonatal rat ventricular cardiomyocytes. On the contrary, the overexpression of ENH3, a LIM-less cardiac-specific splice variant, inhibited the phosphorylation of CREB-Ser133. Concomitantly, both real-time qPCR and promoter assay showed that the overexpression of ENH1 enhanced but ENH3 prevented the transcriptional activation of a CREB-target gene, the immediately early gene c-fos. Finally, we found that ENH1 regulated the translocation of phosphorylated CREB to the nucleus. Taken all together, our results suggest that ENH1 plays an essential role in CREB’s activation and dependent transcription in cardiomyocytes. At the opposite, ENH3 splice variant inhibited the CREB activity in cardiomyocytes. In conclusion, our work describes a new molecular mechanism involving ENH splice variants with opposing functions.

Sign in / Sign up

Export Citation Format

Share Document