Research Paper Volume 11, Issue 12 pp 3909—3918
Alda-1 attenuates hyperoxia-induced mitochondrial dysfunction in lung vascular endothelial cells
- 1 University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, Florida 33612, United States
- 2 University of South Florida, Division of Allergy and Immunology, Department of Molecular Medicine, College of Medicine, Tampa, Florida 33612, United States
- 3 Department of Zoology, Yogi Vemana University, Kadapa, India
received: March 6, 2019 ; accepted: May 31, 2019 ; published: June 17, 2019 ;https://doi.org/10.18632/aging.102012
How to Cite
Copyright: Patil et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Acute lung injury (ALI) is a major cause of morbidity and mortality worldwide, especially in aged populations. Mitochondrial damage is one of the key features of ALI. Hyperoxia-induced lung injury model in mice has been widely used for ALI study because it features many ALI phenotypes including, but not limited to, mitochondrial and vascular endothelial cell damage. Recently, accumulating evidence has shown that mitochondrial aldehyde dehydrogenase 2 (ALDH2) has a protective effect against oxidative stress mediated cell damage in epithelial cells. However, it is not known whether ALDH2 protects against oxidative stress in vascular endothelial cells. In this current study, we attempted to find the capacity of Alda-1 [(N-(1,3benzodioxol-5-ylmethyl)-2,6- dichloro-benzamide), an ALDH2 activator] to protect against oxidative stress in human microvascular endothelial cells (HMVEC). HMVEC pretreated with Alda-1 prior to hyperoxic exposure vs non-treated controls showed i) lower 4-hydroxynonenal (4-HNE) levels, ii) significantly decreased expressions of Bax and Cytochrome C, iii) partially restored activity and expression of ALDH2 and iv) significantly improved mitochondrial membrane potential. These results suggest that ALDH2 protein in lung vascular endothelial cells is a promising therapeutic target for the treatment of ALI and that Alda-1 is a potential treatment option.