Cell-free methemoglobin drives platelets to apoptosis via mitochondrial ROS-mediated activation of JNK and p38 MAP kinase

NaveenKumar, S. K. and Hemshekhar, M. and Sundaram, M. S. and Kemparaju, K. and Girish, K. S. (2017) Cell-free methemoglobin drives platelets to apoptosis via mitochondrial ROS-mediated activation of JNK and p38 MAP kinase. Biochemical and Biophysical Research Communications, 491 (1). pp. 183-191. ISSN 0006-291X

[img] Text (Full Text)
1-s2.0-S0006291X17314158-main.pdf - Published Version
Restricted to Registered users only

Download (2694Kb) | Request a copy
Official URL: https://doi.org/10.1016/j.bbrc.2017.07.073

Abstract

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.

Item Type: Article
Additional Information: Unmapped bibliographic data: PY - 2017/9/9/ [EPrints field already has value set] JO - Biochemical and Biophysical Research Communications [Field not mapped to EPrints]
Uncontrolled Keywords: Apoptosis, JNK-MAP kinase, Methemoglobin, Mitochondrial reactive oxygen species, Platelets
Subjects: Agriculture Biological Sciences > Biochemistry
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biochemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Biochemistry
Depositing User: Praveen Kumari B.L
Date Deposited: 30 Oct 2017 05:10
Last Modified: 30 Oct 2017 05:10
URI: http://eprints.uni-mysore.ac.in/id/eprint/20119

Actions (login required)

View Item View Item