Molecular cloning and oxidative modification of human lens ALDH1A1: Implication in impaired detoxification of lipid aldehydes

Tianlin Xiao, Mohammad Shoeb, M. Saeed Siddiqui, Min Zhang, Kota Ramana, Satish Srivastava, Vasilis Vasiliou, Naseem Ansari

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Earlier studies showed that human lens ALDH1A1 plays a critical role in protection against oxidative stress-induced cytotoxicity in human lens epithelial cells (HLEC), and opacification of rat and mouse lens. The complete coding sequence of ALDH1A1 was cloned from human lens cDNA library by using PCR methods and expressed it in Escherichia coli. The cloned human lens ALDH1A1 cDNA encodes a 501-amino-acid protein (molecular mass = 54.8 kD) that is 100% identical to human liver ALDH1A1 and shares significant identity with the same isozyme from other tissues and species. The purified recombinant human lens ALDH1A1 exhibited optimal catalytic activity at pH 8 and preferred NAD+ as cofactor and specifically catalyzed the oxidation of toxic lipid aldehydes such as 4-hydroxynonenal (HNE; Km = 4.8 mM) and malonaldehyde (Km MDA = 3.5 mM). Citral, disulfiram, and cyanamide were found to inhibit human lens ALDH1A1 at IC50 values of 55, 101, and 22610 μM, respectively, whereas diethylstilbestrol (DES) was found to be an activator (EC50, 1.3 μM). Further, modification of recombinant human lens ALDH1A1 with nitric oxide donors such as S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) significantly inhibited the enzyme activity. It therefore appears that activation of ALDH1A1, which efficiently catalyzes the detoxification of lipid-derived toxic aldehydes, and/or prevention of its oxidative modification may be novel therapeutic interventions against oxidative stress-induced lens pathologies.

Original languageEnglish (US)
Pages (from-to)577-584
Number of pages8
JournalJournal of Toxicology and Environmental Health - Part A: Current Issues
Volume72
Issue number9
DOIs
StatePublished - 2009

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Detoxification
Cloning
Molecular Cloning
Aldehydes
Lenses
Lipids
citral
Oxidative stress
Poisons
Oxidative Stress
Cyanamide
S-Nitrosoglutathione
S-Nitroso-N-Acetylpenicillamine
Disulfiram
Diethylstilbestrol
Nitric Oxide Donors
Enzyme activity
Molecular mass
Pathology
Cytotoxicity

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Molecular cloning and oxidative modification of human lens ALDH1A1 : Implication in impaired detoxification of lipid aldehydes. / Xiao, Tianlin; Shoeb, Mohammad; Siddiqui, M. Saeed; Zhang, Min; Ramana, Kota; Srivastava, Satish; Vasiliou, Vasilis; Ansari, Naseem.

In: Journal of Toxicology and Environmental Health - Part A: Current Issues, Vol. 72, No. 9, 2009, p. 577-584.

Research output: Contribution to journalArticle

Xiao, Tianlin ; Shoeb, Mohammad ; Siddiqui, M. Saeed ; Zhang, Min ; Ramana, Kota ; Srivastava, Satish ; Vasiliou, Vasilis ; Ansari, Naseem. / Molecular cloning and oxidative modification of human lens ALDH1A1 : Implication in impaired detoxification of lipid aldehydes. In: Journal of Toxicology and Environmental Health - Part A: Current Issues. 2009 ; Vol. 72, No. 9. pp. 577-584.
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AU - Zhang, Min

AU - Ramana, Kota

AU - Srivastava, Satish

AU - Vasiliou, Vasilis

AU - Ansari, Naseem

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