Mariotto Sofia, Cavalieri Elisabetta, Amelio Ernesto, Ciampa Anna Rosa, de Prati Alessandra Carcereri, Marlinghaus Ernst, Russo Sergio, Suzuki Hisanori
Department of Neuroscience and Vision, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
Nitric Oxide. 2005 Mar;12(2):89-96. doi: 10.1016/j.niox.2004.12.005.
At low energy density (0.03 mJ/mm2), extracorporeal shock waves (ESW), originally developed for clinical lithotripsy, have successfully been used for anti-inflammatory treatment of soft tissues. Since nitric oxide plays a critical role in inflammation, we hypothesized for ESW to increase NO production in cells. Using human umbilical vein endothelial cells as a model system, we observed that ESW, at low energy density, rapidly induced an enhancement of eNOS activity. In these cells, eNOS activity is modulated by tyrosine- and serine-phosphorylation. ESW shifted eNOS to a less-tyrosine-phosphorylated form, without affecting its serine-phosphorylation, thus accounting for its rapid enzyme activation. LPS/IFN-gamma treatment of human umbilical vein endothelial cells induced a rapid inhibition of eNOS activity and concomitant NF-kappaB activation which were efficiently counteracted by ESW treatment. Therefore, the present results indicate that the molecular mechanism of clinically observed anti-inflammatory action of ESW should include tyrosine-dephosphorylation of eNOS, a successive increase in NO production and suppression of NF-kappaB activation.
在低能量密度（0.03毫焦/平方毫米）下，最初为临床碎石术开发的体外冲击波（ESW）已成功用于软组织的抗炎治疗。由于一氧化氮在炎症中起关键作用，我们推测ESW可增加细胞中一氧化氮的产生。以人脐静脉内皮细胞作为模型系统，我们观察到低能量密度的ESW能迅速诱导内皮型一氧化氮合酶（eNOS）活性增强。在这些细胞中，eNOS活性受酪氨酸和丝氨酸磷酸化调节。ESW使eNOS转变为酪氨酸磷酸化程度较低的形式，而不影响其丝氨酸磷酸化，从而解释了其酶的快速激活。用脂多糖（LPS）/γ干扰素处理人脐静脉内皮细胞可迅速抑制eNOS活性并伴随核因子κB（NF-κB）激活，而ESW处理可有效对抗这种情况。因此，目前的结果表明，临床上观察到的ESW抗炎作用的分子机制应包括eNOS的酪氨酸去磷酸化、一氧化氮产生的相继增加以及NF-κB激活的抑制。
