Miletic Gordana, Hanson Eric N, Savagian Caitlin A, Miletic Vjekoslav
Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706-1102, USA.
Neurosci Lett. 2004 Apr 29;360(3):149-52. doi: 10.1016/j.neulet.2004.02.060.
We examined whether early injury-associated activation of cyclic AMP response element binding protein (CREB) in the spinal dorsal horn was mediated by the cyclic AMP-dependent protein kinase A (PKA) pathway. Significant increases in the levels of phosphorylated CREB (pCREB), phosphorylated PKAIIalpha regulatory subunit (pPKA), and PKAalpha catalytic subunit (PKAalpha cat) were elicited 2 h after loose ligation of the sciatic nerve. These injury-elicited increases were significantly reduced by dorsal horn application of the cell-permeable PKA inhibitor Rp-8-Br-cAMPS. The cell-permeable PKA activator Sp-8-Br-cAMPS significantly increased the levels of pCREB, pPKA and PKAalpha cat 2 h after application onto the dorsal horn of control, uninjured animals. Our data lent further support to the notion that activation of PKA may play an important role in the early stages of nerve injury-elicited plasticity in the dorsal horn.
我们研究了脊髓背角中早期损伤相关的环磷酸腺苷反应元件结合蛋白（CREB）激活是否由环磷酸腺苷依赖性蛋白激酶A（PKA）途径介导。坐骨神经松弛结扎2小时后，磷酸化CREB（pCREB）、磷酸化PKAIIα调节亚基（pPKA）和PKAα催化亚基（PKAα cat）水平显著升高。背角应用细胞可渗透的PKA抑制剂Rp-8-Br-cAMPS可显著降低这些损伤引起的升高。在对照未受伤动物的背角应用细胞可渗透的PKA激活剂Sp-8-Br-cAMPS 2小时后，pCREB、pPKA和PKAα cat水平显著升高。我们的数据进一步支持了PKA激活可能在背角神经损伤引发的可塑性早期阶段起重要作用这一观点。
