Hemoglobin alpha is a redox-sensitive mitochondrial-related protein in T-lymphocytes.

Autor: Reed EC; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Silva VA; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Giebel KR; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Natour T; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Lauten TH; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Jojo CN; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Schlieker AE; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA., Case AJ; Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA; Department of Medical Physiology, Texas A&M University, Bryan, TX, USA. Electronic address: acase@tamu.edu.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2024 Nov 23; Vol. 227, pp. 1-11. Date of Electronic Publication: 2024 Nov 23.
DOI: 10.1016/j.freeradbiomed.2024.11.044
Abstrakt: Hemoglobin subunits, which form the well-characterized, tetrameric, oxygen-carrying protein, have recently been described to be expressed in various non-canonical cell types. However, the exact function of hemoglobin subunits within these cells remains to be fully elucidated. Herein, we report for the first time, the expression of hemoglobin alpha-a1 (Hba-a1) in T-lymphocytes and describe its role as a mitochondrial-associated antioxidant. Within naïve T-lymphocytes, Hba-a1 mRNA and HBA protein are present and highly induced by redox perturbations, particularly those arising from the mitochondria. Additionally, preliminary data using a T-lymphocyte specific Hba-a1 knock-out mouse model indicated that the loss of Hba-a1 led to an exacerbated production of mitochondrial reactive oxygen species and inflammatory cytokines after a stress challenge, further supporting the role of HBA acting to buffer the mitochondrial redox environment. Interestingly, we observed Hba-a1 expression to be significantly upregulated or downregulated depending on T-lymphocyte polarization and metabolic state, which appeared to be controlled by both transcriptional regulation and chromatin remodeling. Altogether, these data suggest Hba-a1 may function as a crucial mitochondrial-associated antioxidant and appears to possess critical and complex functions related to T-lymphocyte activation and differentiation.
Competing Interests: Declaration of competing interests The authors have declared that no conflict of interest exists.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE