Hofmann Matthias, Zaper Julijana, Bernd August, Bereiter-Hahn Jürgen, Kaufmann Roland, Kippenberger Stefan
Department of Dermatology and Venerology, University Hospital, Johann Wolfgang Goethe-University, D-60590 Frankfurt/Main, Germany.
Biochem Biophys Res Commun. 2004 Apr 9;316(3):673-9. doi: 10.1016/j.bbrc.2004.02.101.
Mechanical stimulation is known to modulate cell physiology in a variety of different tissues. Particularly, epithelial cells are permanently exposed to mechanical stimulation generated by externally applied forces. The present in vitro study demonstrated mechanical pressure as a trigger-factor of the p38 mitogen-activated protein kinase (MAPK) pathway in epithelial cells. Mechanical pressure applied by teflon weights (1.02g/cm(2)) led to a rapid phosphorylation of p38 peaking between 5 and 10min. Furthermore, phosphorylation of the small heat shock protein 27 (HSP27) was shown in response to mechanical pressure. Suppression of p38 function by using specific inhibitors blocked the pressure-mediated phosphorylation of HSP27. In order to identify upstream regulators of p38, a contribution of Src and protein kinase C (PKC) in pressure-signaling was investigated. We could demonstrate that inhibition of Src or PKC suppressed the pressure-induced phosphorylation of p38. These findings suggest mechanical pressure as a new type of effector stimulus for the p38 pathway with implications to (patho-) physiological conditions.
已知机械刺激可调节多种不同组织中的细胞生理。特别是，上皮细胞会持续受到外部施加力产生的机械刺激。目前的体外研究表明，机械压力是上皮细胞中p38丝裂原活化蛋白激酶（MAPK）途径的触发因素。由聚四氟乙烯重物（1.02g/cm²）施加的机械压力导致p38迅速磷酸化，在5至10分钟之间达到峰值。此外，还显示小热休克蛋白27（HSP27）会响应机械压力而发生磷酸化。使用特异性抑制剂抑制p38功能可阻断压力介导的HSP27磷酸化。为了确定p38的上游调节因子，研究了Src和蛋白激酶C（PKC）在压力信号传导中的作用。我们可以证明，抑制Src或PKC可抑制压力诱导的p38磷酸化。这些发现表明机械压力是p38途径的一种新型效应刺激，对（病理-）生理状况具有影响。
