Importance of inverse correlation between ALDH3A1 and PPARgamma in tumor cells and tissue regeneration

Aldehyde dehydrogenase (ALDH) enzymes are involved in maintaining cellular homeostasis by metabolizing both endogenous and exogenous reactive aldehydes. They modulate several cell functions including proliferation, differentiation, survival as well as cellular response to oxidative stress. We previously reported that ALDH3A1 expression is inversely correlated with the activation of PPARs (Peroxisome Proliferators-Activated Receptors), a category of orphan nuclear hormone receptors, in both rat and human cells. PPARgamma is involved in cell proliferation. In this study, we have used PPARgamma transfection and inhibition to examine the relationship between ALDH3A1 and PPARgamma and their role as regulators of cell proliferation. Induction of PPARgamma in A549 and NCTC 2544 cells by transfection caused a decrease in ALDH3A1 and inhibition of cell proliferation, a result we obtained previously using ligands that induce PPAR. A reduction of PPARgamma expression using siRNA increased ALDH3A1 expression and cell proliferation. In cells induced to proliferate in a model of tissue regeneration, ALDH3A1 expression increased during the period of proliferation, whereas PPARgamma expression decreased. In conclusion, through modulation of PPARgamma or ALDH3A1, it may be possible to reduce cell proliferation in tumor cells or stimulate cell proliferation in normal cells during tissue regeneration.