Role of Aldehyde Dehydrogenase Isozymes in the Defense of Rat Lens and Human Lens Epithelial Cells against Oxidative Stress

Abstract

The results suggest that, under oxidative stress, HNE produced in the lens epithelium can cause toxicity and thus contribute to oxidation-induced cataractogenesis. Furthermore, the studies indicate that ALDH1A1 is a critical isozyme for maintaining clarity in human, rat, and mouse lenses.

Mitochondrion as a Novel Site of Dichloroacetate Biotransformation by Glutathione Transferase ζ1

“…Furthermore, increased production of reactive oxygen species and lipid peroxidation have been demonstrated in the livers of mice treated with high doses of DCA (Larson and Bull, 1992;Hassoun et al, 2010). Overexpression of ALDH1A1 has been shown to be an adaptive response to oxidative stress (Choudhary et al, 2005;Leonard et al, 2006). Therefore, we tentatively attribute the induced expression of cytosolic ALDH1A1 to be a secondary response to DCA exposure.…”

Self-regulatory role of 4-hydroxynonenal in signaling for stress-induced programmed cell death

“…The induction of Fas-mediated signaling for apoptosis by HNE suggests that signaling by membrane proteins of different gene families (e.g., death receptors, EGFR, RalBP1) can be propagated by HNE. Further studies on the consequences of the interactions of HNE with the membrane-associated, cytoplasmic, and nuclear proteins should provide clues to the mechanisms through which HNE causes such a multitude of effects on various cellular processes reported over the years [1][2][3][4][5][6][7][8][9].…”

“…The enzymes such as glutathione S-transferases, aldehyde dehydrogenases, and aldose reductases and transporters such as RalBP1 and MRP1 that catalyze the efflux of its metabolites regulate its intracellular concentrations [2][3][4][5][6][7][8][9][10][11][12][13][14][15]. GSTs catalyze the conjugation of HNE to glutathione (GSH) which is the major pathway for disposition of HNE.…”

“…These studies have opened a new area in the field of ROS-induced signaling focusing on the regulatory roles of the enzymes involved in the formation and metabolism of HNE. Recent studies in this area have shown that enzymes such as glutathione S-transferases (GSTs), aldehyde dehydrogenases, aldose reductase, glutathione peroxidase, and RalBP1 (Ral-binding protein 1) that are among the major determinants of intracellular levels of HNE can modulate stress-induced signaling for programmed cell death [2][3][4][5][6][7][8][9][10]. Some of these studies [11][12][13][14] seem to have major clinical implications particularly in regard to cancer chemotherapy [11,12], inhibition of tumor growth [13], and sepsis [14] as discussed briefly later in this review.…”

Potential applications for RNAi to probe pathogenesis and develop new treatments for ocular disorders

“…This strategy has been used to explore the function of microsomal glutathione S-transferase 1 in protection of RPE cells from oxidative stress, 29 the effect of loss of mitochondrial DNA sequences on RPE cells, 30 the role of NeuroD in photoreceptor formation, 31 the role of stem cell factor/c-Kit in tumorigenesis of uveal melanocytes, 32 the role of aldehyde dehydrogenase isozymes or methionine sulfoxide reductase A in oxidative defense of lens cells, 33,34 the role of eukaryotic translation initiation factor 5A on tumor necrosis factora-induced apoptosis of lamina cribosa cells, 35 survivalpromoting effects of hepatocyte growth factor on corneal epithelial cells, 36 the role of 1Na + -3HCO 3 À cotransporter in HCO 3 À flux in corneal endothelial cells, 37 TGFb2-induced production of extracellular matrix by astrocytes derived from optic nerve, 38 and regulation of eye development by transcriptional control of CCCTC binding factor. 39 …”