Alda-1 shields endothelial cells against oxidative stress via activation of ALDH2
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Sahebgowda S. Patil, B.S., Venkata Ramireddy Narala, Ph.D., Helena Hernández-Cuervo, M.D., Byeong J. Cha, Ph.D., Jutaro Fukumoto, M.D. and Ph.D., Mason T. Breitzig, B.S., Richard F. Lockey, M.D., Narasaiah Kolliputi, PhD, Lakshmi Galam, Ph.D.

Endothelial dysfunction and change in vascular permeability are key events in many allergic diseases including edema and chronic obstructive pulmonary disease (COPD). On the molecular level, mitochondrial dysfunction contributes to the elevation of reactive oxygen species (ROS), which can then destabilize mitochondrial membrane potential. Now, research demonstrates that aldehyde dehydrogenase 2 (ALDH2) could be an invaluable combatant against mitochondrial dysfunction. Human carriers possessing an inactive ALDH2 variant have been found to be more susceptible to COPD and asthma. The novel specific activator of ALDH2, Alda-1, shields against cellular damage in diseases such as ischemia reperfusion and heart failure. Administration of this potent activator may sufficiently amplify ALDH2 activity and attenuate endothelial dysfunction in pulmonary diseases.


Human microvascular endothelial cells (lung; HMVECs) were seeded and, after reaching confluence, treated with DMSO and Alda-1 along with exposure to normoxia or hyperoxia at different time points. After every 24, 48, and 72 hours, the cells were collected for mitochondrial analyses assessing mitochondrial permeability (JC1 staining), ROS (MitoSox), Cytochrome C release, as well as ALDH2 activity (ELISA) and expression (Western blot).


Cells treated with Alda-1 displayed elevated ALDH2 activity in normoxia and hyperoxia. We also noted that Alda-1 rescued mitochondrial membrane potential, decreased Cytochrome C release, and suppressed mitochondrial ROS production in HMVECs.


Our findings suggest that Alda-1-mediated modulation of ALDH2 is a significant target for remediation of endothelial dysfunction through preservation of mitochondria. These results reveal a promising therapeutic approach to treating allergic diseases where endothelial dysfunction is a characteristic event.