Stimulation of fibroblast proliferation by neokyotorphin requires Ca2+ influx and activation of PKA, CaMK II and MAPK/ERK
Stimulation of fibroblast proliferation by neokyotorphin requires Ca2+ influx and activation of PKA, CaMK II and MAPK/ERK
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DOI：
10.1111/j.1742-4658.2006.05594.x
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发表时间：
2007-01
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影响因子：
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通讯作者：
O. Sazonova;E. Blishchenko;Anna G. Tolmazova-;Dmitry P. Khachin-;Konstantin V. Leontiev;A. A. Karelin-A.;Vadim T. Ivanov-Va
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文献类型：
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作者：
O. Sazonova;E. Blishchenko;Anna G. Tolmazova-;Dmitry P. Khachin-;Konstantin V. Leontiev;A. A. Karelin-A.;Vadim T. Ivanov-Va
Neokyotorphin [TSKYR，血红蛋白 α 链片段 (137-141)] 先前已被证明可以增强成纤维细胞增殖，其效果取决于细胞密度和血清水平。在这里，我们展示了新京都啡对细胞类型的影响及其与蛋白激酶 A (PKA) 激活剂 8-Br-cAMP 的影响的相关性，但与 PKC 激活剂 4β-佛波醇 12-肉豆蔻酸酯、13-乙酸酯 (PMA) 的影响无关。在L929成纤维细胞中，新京都啡肽的增殖作用被Ca2+L型通道抑制剂维拉帕米或硝苯地平、细胞内Ca2+螯合剂1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸乙酰氧基甲酯、激酶抑制剂H-89 (PKA)、KN-62抑制（Ca2+/钙调蛋白依赖性激酶 II）和 PD98059（丝裂原激活蛋白激酶）。 KN-62 和 PD98059 也抑制 8-Br-cAMP 的增殖作用。 PKC 抑制（用 PMA 下调或用双吲哚马来酰亚胺 XI 抑制）不影响新京都啡的作用。获得的结果表明新京都啡具有类似 cAMP 的作用。
Neokyotorphin [TSKYR, hemoglobin α‐chain fragment (137–141)] has previously been shown to enhance fibroblast proliferation, its effect depending on cell density and serum level. Here we show the dependence of the effect of neokyotorphin on cell type and its correlation with the effect of protein kinase A (PKA) activator 8‐Br‐cAMP, but not the PKC activator 4β‐phorbol 12‐myristate, 13‐acetate (PMA). In L929 fibroblasts, the proliferative effect of neokyotorphin was suppressed by the Ca2+L‐type channel inhibitors verapamil or nifedipine, the intracellular Ca2+ chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid acetoxymethyl ester, kinase inhibitors H‐89 (PKA), KN‐62 (Ca2+/calmodulin‐dependent kinase II) and PD98059 (mitogen‐activated protein kinase). The proliferative effect of 8‐Br‐cAMP was also suppressed by KN‐62 and PD98059. PKC suppression (downregulation with PMA or inhibition with bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained point to a cAMP‐like action for neokyotorphin.