Alda-1 Attenuates Hyperoxia-induced Mitochondrial Dysfunction in Lung Vascular Endothelial Cells

Authors

Sahebgowda Sidramagowda Patil, University of South Florida
Helena Hernández-Cuervo, University of South Florida
Jutaro Fukumoto, University of South FloridaFollow
Venkata Ramireddy Narala, Yogi Vemana University
Smita Saji, University of South Florida
Monica Borra, University of South Florida
Matthew Alleyn, University of South Florida
Muling Lin, University of South Florida
Ramani Soundararajan, University of South FloridaFollow
Richard Lockey, University of South FloridaFollow
Narasaiah Kolliputi, University of South FloridaFollow
Lakshmi Galam, University of South FloridaFollow

Document Type

Article

Publication Date

2019

Digital Object Identifier (DOI)

https://doi.org/10.18632/aging.102012

Abstract

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.

Rights Information

This work is licensed under a Creative Commons Attribution 3.0 License.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Aging, v. 11, issue 12, p. 3908-3918

Scholar Commons Citation

Patil, Sahebgowda Sidramagowda; Hernández-Cuervo, Helena; Fukumoto, Jutaro; Narala, Venkata Ramireddy; Saji, Smita; Borra, Monica; Alleyn, Matthew; Lin, Muling; Soundararajan, Ramani; Lockey, Richard; Kolliputi, Narasaiah; and Galam, Lakshmi, "Alda-1 Attenuates Hyperoxia-induced Mitochondrial Dysfunction in Lung Vascular Endothelial Cells" (2019). Internal Medicine Faculty Publications. 186.
https://digitalcommons.usf.edu/intmed_facpub/186