NaveenKumar Somanathapura K, Hemshekhar Mahadevappa, Sundaram Mahalingam S, Kemparaju Kempaiah, Girish Kesturu S
Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysuru 570 006, India.
Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysuru 570 006, India; Department of Internal Medicine, Manitoba Centre for Proteomics and Systems Biology, University of Manitoba, Winnipeg R3E3P4, Canada.
Biochem Biophys Res Commun. 2017 Sep 9;491(1):183-191. doi: 10.1016/j.bbrc.2017.07.073. Epub 2017 Jul 13.
Cell-free hemoglobin (Hb), a well-known marker of intravascular hemolysis, is eventually oxidized to methemoglobin (MtHb). Elevated levels of MtHb have been noted, alongside depleted levels of platelets, in several hemolytic diseases. The current study aims to probe the possible role of MtHb in platelet death, based on the facts that it is a pro-inflammatory and pro-apoptotic agent, as well as the sensitive nature of platelets and their tendency to undergo apoptosis under oxidative stress. An attempt is made to establish the link between hemolysis and thrombocytopenia, by deciphering the underlying molecular signaling pathways. The results of this study demonstrate that MtHb, not Hb exerts oxidative stress on platelets, which triggers their death via ROS-mediated mitochondrial apoptotic pathway. It was further established that the MtHb-induced platelet apoptotic events mediate through JNK and p38 MAPK activation. Thus, the study presents a mechanistic insight into the previous studies that reported the incidence of thrombocytopenia in hemolytic diseases. This study highlights the fate of platelets in intravascular hemolytic conditions, which demands the need for a specific treatment strategy considering the risks associated with thrombocytopenia during severe hemolytic diseases.
游离血红蛋白（Hb）是血管内溶血的一个众所周知的标志物，最终会被氧化为高铁血红蛋白（MtHb）。在几种溶血性疾病中，已观察到MtHb水平升高，同时血小板水平降低。基于MtHb是一种促炎和促凋亡因子，以及血小板的敏感性及其在氧化应激下易于发生凋亡的特性，本研究旨在探究MtHb在血小板死亡中的可能作用。通过解读潜在的分子信号通路，试图建立溶血与血小板减少之间的联系。本研究结果表明，对血小板施加氧化应激的是MtHb而非Hb，它通过活性氧（ROS）介导的线粒体凋亡途径触发血小板死亡。进一步确定，MtHb诱导的血小板凋亡事件是通过JNK和p38丝裂原活化蛋白激酶（MAPK）的激活介导的。因此，本研究为先前报道溶血性疾病中血小板减少发生率的研究提供了机制上的见解。这项研究突出了血管内溶血情况下血小板的命运，这就需要考虑到严重溶血性疾病期间与血小板减少相关的风险，制定一种特定的治疗策略。
