Involvement of aldose reductase in the metabolism of atherogenic aldehydes

Sanjay Srivastava, Si Qi Liu, Daniel J. Conklin, Albert Zacarias, Satish K. Srivastava, Aruni Bhatnagar

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Phospholipid peroxidation generates a variety of aldehydes, which includes free saturated and unsaturated aldehydes, and aldehydes that remain esterified to the phosphoglyceride backbone - the so-called 'core' aldehydes. However, little is known in regarding the vascular metabolism of these aldehydes. To identify biochemical pathways that metabolize free aldehydes, we examined the metabolism of 4-hydroxy-trans-2-nonenal in human aortic endothelial cells. Incubation of these cells with [3H]-HNE led to the generation of four main metabolites, i.e. glutathionyl HNE (GS-HNE), glutathionyl dihydroxynonene (GS-DHN), DHN and 4-hydroxynonanoic acid (HNA), which accounted for 5, 50, 6, and 23% of the total HNE metabolized. The conversion of GS-HNE to GS-DHN was inhibited by tolrestat, indicating that it is catalyzed by aldose reductase (AR). The AR was also found to be an efficient catalyst for the reduction of the core aldehyde - 1-palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine, which is generated in minimally modified low-density lipoprotein, and activates the endothelium to bind monocytes. As determined by electrospray mass spectrometry, reduction of POVPC (m/z=594) by AR led to the formation of 1-palmitoyl-2- (5)-hydrovaleryl-sn-glycero-3-phosphorylcholine (PHVPC; m/z=596). These observations suggest that due to its ability to catalyze the reduction of lipid-derived aldehydes AR may be involved in preventing inflammation and diminishing oxidative stress during the early phases of atherogenesis.

Original languageEnglish (US)
Pages (from-to)563-571
Number of pages9
JournalChemico-Biological Interactions
StatePublished - Jan 30 2001
Externally publishedYes


  • 1-Palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine
  • 4-Hydroxy-trans-2-nonenal
  • Aldose reductase
  • Atherosclerosis
  • Lipid peroxidation

ASJC Scopus subject areas

  • Toxicology


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