期刊
BIOCHEMICAL JOURNAL
卷 364, 期 -, 页码 73-79出版社
PORTLAND PRESS
DOI: 10.1042/bj3640073
关键词
brown adipocyte; cirazoline; noradrenaline; norepinephrine; PMA
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 less than or equal to 5 min with slow decay) and efficiently (EC50 6 nM). The increase in CREB phosphorylation coincided with increased expression of an artificial cAMP-response-clement-containing reporter construct, CREB phosphorylation was partly inhibitable, both by the /3-adrenergic antagonist propranolol and by the alpha(1)-adrenergic antagonist prazosin. Adenylate cyclase hyperactivation (by forskolin) could stimulate CREB phosphorylation to the same extent as noradrenaline. The alpha(1)-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 (alpha(1)-adrenergic) CREB phosphorylation was inhibited by a desensitizing pretreatment with PMA, demonstrating that the alpha(1)-stimulation was mediated via protein kinase C activation; neither Src nor extracellular-signal-regulated kinases I and 2 activation was involved in the signalling process. We conclude that CREB phosphorylation in brown adipocytes is mediated not only through the classical beta-adrenergic/cAMP pathway but also through a novel alpha(1)-adrenergic/protein kinase C/CREB pathway, which has not been described previously in any tissue.
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