Expression and activity of paraoxonase 1 in human cataractous lens tissue.
Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that is believed to be involved in the protection against oxidative stress. There is evidence that paraoxonase activity is reduced in patients with diabetes and cataract. In the current study, we analyzed mRNA expression of PON1 as well as other members of the paraoxonase family, PON2 and PON3, in human cataractous lens samples. Our results indicate that only PON1 is expressed at the gene and protein levels in human lens tissues. We quantified MDA levels and measured PON1 (paraoxonase/arylesterase) enzymatic activities in subjects suffering from cataract due to aging and diabetes. Decreased PON1 activity was more pronounced in diabetic patients (p< 0.001) compared to senile subjects, which may be due to glycation and increased oxidative insult. To examine the structural alterations that occur in response to glycation, we constructed a three-dimensional model of PON1 and its glycated variant. Glycation at Lys70 and Lys75 is predicted to cause hindrance in binding of substrate to the active site of the enzyme.
Hashim
Zehra
Z
Department of Biochemistry, University of Karachi, Karachi, Pakistan.
Ilyas
Amber
A
Saleem
Ammara
A
Salim
Asmat
A
Zarina
Shamshad
S
D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D002386:Cataract / Q000201:enzymology* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004950:Esterases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced; D006801:Humans; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000201:enzymology* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008875:Middle Aged; D008956:Models, Chemical; D018384:Oxidative Stress; D013379:Substrate Specificity
D017127:Glycation End Products, Advanced; D008315:Malondialdehyde; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; C468411:PON2 protein, human; C113656:PON3 protein, human