Tong L J, Dong L W, Liu M S
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Missouri, USA.
Mol Cell Biochem. 1998 Dec;189(1-2):55-61. doi: 10.1023/a:1006804429027.
Effects of GTP-binding proteins on the activation of secretory phospholipaseA2 (sPLA2) and cytosolic phospholipaseA2 (cPLA2) in rat liver during two different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. The results show that in the absence of G-protein modulator, hepatic sPLA2 and cPLA2 activities were activated by 40.8-46 and 91.6-105.8%, respectively, during early and late phases of sepsis. GTPgammaS and fluoroaluminate (AlF4-) stimulated sPLA2 and cPLA2 activities within each experimental group, i.e., control, early sepsis, and late sepsis. The GTPgammaS and AlF4(-)-stimulated sPLA2 and cPLA2 activities remained significantly elevated during early phase (22.3-65.6% increase) and late phase (32.5-109.1% increase) of sepsis. Further analyses demonstrate that cholera toxin significantly stimulated sPLA2 and cPLA2 activities within each experimental group, and that the cholera toxin stimulated sPLA2 and cPLA2 activities remained significantly higher during early phase (23.5-37% increase) and late phase (56.7-70% increase) of sepsis. In contrast, pertussis toxin significantly inhibited sPLA2 and cPLA2 activities within each experimental group, and that the pertussis toxin-inhibited sPLA2 and cPLA2 activities remained significantly higher in early septic (57-68.5% increase) and late septic (34.6-45.5% increase) experiments. These data demonstrate that cholera toxin-sensitive G alpha s and pertussis toxin-sensitive G alpha i were both involved in the activation of sPLA2 and cPLA2 activities in rat liver during the progression of sepsis.
研究了GTP结合蛋白在脓毒症两个不同阶段对大鼠肝脏中分泌型磷脂酶A2（sPLA2）和胞质型磷脂酶A2（cPLA2）激活的影响。通过盲肠结扎和穿刺（CLP）诱导脓毒症。实验分为三组：对照组、早期脓毒症组和晚期脓毒症组。早期和晚期脓毒症分别指CLP后9小时和18小时处死的动物。结果显示，在不存在G蛋白调节剂的情况下，脓毒症早期和晚期肝脏sPLA2和cPLA2活性分别被激活40.8 - 46%和91.6 - 105.8%。GTPγS和氟铝酸盐（AlF4-）在每个实验组（即对照组、早期脓毒症组和晚期脓毒症组）中均刺激sPLA2和cPLA2活性。在脓毒症早期（增加22.3 - 65.6%）和晚期（增加32.5 - 109.1%），GTPγS和AlF4(-)刺激的sPLA2和cPLA2活性仍显著升高。进一步分析表明，霍乱毒素在每个实验组中均显著刺激sPLA2和cPLA2活性，且在脓毒症早期（增加23.5 - 37%）和晚期（增加56.7 - 70%），霍乱毒素刺激的sPLA2和cPLA2活性仍显著更高。相反，百日咳毒素在每个实验组中均显著抑制sPLA2和cPLA2活性，且在早期脓毒症（增加57 - 68.5%）和晚期脓毒症（增加34.6 - 45.5%）实验中，百日咳毒素抑制的sPLA2和cPLA2活性仍显著更高。这些数据表明，霍乱毒素敏感的Gαs和百日咳毒素敏感的Gαi在脓毒症进展过程中均参与了大鼠肝脏中sPLA2和cPLA2活性的激活。
