Protein Disulfide Isomerase and Sulfhydryl-Dependent Pathways in Platelet Activation

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• 作者：David W. Essex ; Mengru Li ; Anna Miller ; and Richard D. Feinman
• 刊名：Biochemistry
• 出版年：2001
• 出版时间：May 22, 2001
• 年：2001
• 卷：40
• 期：20
• 页码：6070 - 6075
• 全文大小：80K
• 年卷期：v.40,no.20(May 22, 2001)
• ISSN：1520-4995

文摘

The inhibition of blood platelet aggregation and secretion was studied using covalent thiolreagents, maleimides, or mercuribenzoates, or using inhibitors of protein disulfide isomerase (PDI),bacitracin or antibodies to PDI. As expected, both types of inhibitors were effective against stimulationby normal physiologic stimuli. On the other hand, when stimulation was initiated with the peptideLSARLAF, that specifically activates the integrin mages/gifchars/alpha.gif" BORDER=0>IIbmages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">3 (the fibrinogen receptor), the PDI inhibitorswere without effect. LSARLAF-induced aggregation was, however, inhibited by the sulfhydryl reagents.To further investigate the role of sulfhydryl-containing proteins and mages/gifchars/alpha.gif" BORDER=0>IIbmages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">3, platelets were labeled withmembrane-impermeant sulfhydryl reagents. Nine bands were found labeled on gel electrophoresis. Twoof the labeled bands were identified as mages/gifchars/alpha.gif" BORDER=0>IIb and mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">3. The conclusions are that while PDI is required forplatelet aggregation and secretion, an additional sulfhydryl-dependent step or protein is also required.This latter reaction occurs at the level of mages/gifchars/alpha.gif" BORDER=0>IIbmages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">3. In distinction to most literature reports, at least asubpopulation of mages/gifchars/alpha.gif" BORDER=0>IIbmages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">3 contains free sulfhydryl groups, consistent with the possibility that it is a substratefor PDI or part of the sulfhydryl-dependent response.