GHRP-6 Induces CREB Phosphorylation and Growth Hormone Secretion via a Protein Kinase Cσ-dependent Pathway in GH3 Cells
10.1007/s11596-010-0210-5
- Author:
TIAN CHUNLEI
1
;
YE FEI
;
XU TONGJIANG
;
WANG SHENG
;
WANG XIAODAN
;
WANG HEPING
;
WAN FENG
;
LEI TING
Author Information
1. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- Keywords:
growth hormone secretagogues;
protein kinase C;
CREB;
growth hormone
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2010;30(2):183-187
- CountryChina
- Language:Chinese
-
Abstract:
This study examined the effect of GHRP-6,a known GHSs receptor agonist,on the phosphorylation of cAMP-responsive clement-binding protein(CREB)and the underly mechanism.GH3 cells were cultured and subjected to different treatments as follows: GHRP-6,GHRP-6 plus GHRH,phorbol ester(PMA),an activator of PKC,alone or in combination with GHRP-6,G(o)6983,a general inhibitor of PKCs,in the presence or absence of GHRP-6,rottlerin,an inhibitor of PKCs,alone or plus GHRP-6.The cells were transiently transfected with PKCσ-specific siRNA and then treated with GHRP-6.GH level was measured by enzyme-linked immunosorbent assay(ELISA).The expression of phosphor-CREB,PKCσ,PKCθ and phosphor-PKCσ was determined by Western blotting.The results showed that GHRP-6 stimulated GH secretion in both time-and dose-dependent manners and enhanced the effect of GHRH on GH secretion.GHRP-6 was also found to induce CREB phosphorylation.Moreover,GH secretion was enhanced by the PKC activator PMA and reduced by the PKC inhibitors(G(o)6983,rottlerin)and knockdown of PKCσ.PKCσ could be activated by GHRP-6.It is concluded that PKC,especially PKCσ,mediates CREB phosphorylation and GHRP-6-induced GH secretion.
