Biomaterial Database

Exploration of molecular factors impairing superoxide dismutase isoforms activity in human senile cataractous lenses. 2013

Sankaranarayanan Rajkumar, and Abhay R Vasavada, and Mamidipudi R Praveen, and Rajendran Ananthan, and Geereddy B Reddy, and Harsha Tripathi, and Darshini A Ganatra, and Anshul I Arora, and Alpesh R Patel

Department of Molecular Genetics and Biochemistry, Iladevi Cataract and IOL Research Centre, Memnagar, Ahmedabad, Gujarat, India.

OBJECTIVE To explore different molecular factors impairing the activities of superoxide dismutase (SOD) isoforms in senile cataractous lenses. METHODS Enzyme activity of SOD isoforms, levels of their corresponding cofactors copper (Cu), manganese (Mn), zinc (Zn), and expression of mRNA transcripts and proteins were determined in the lenses of human subjects with and without cataract. DNA from lens epithelium (LE) and peripheral blood was isolated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by sequencing was carried out to screen somatic mutations. The impact of intronic insertion/deletion (INDEL) variations on the splicing process and on the resultant transcript was evaluated. Genotyping of IVS4+42delG polymorphism of SOD1 gene was done by PCR-restriction fragment length polymorphism (RFLP). RESULTS A significant decrease in Cu/Zn- and Mn-SOD activity (P < 0.001) and in Cu/Zn-SOD transcript (P < 0.001) and its protein (P < 0.05) were found in cataractous lenses. No significant change in the level of copper (P = 0.36) and an increase in the level of manganese (P = 0.01) and zinc (P = 0.02) were observed in cataractous lenses. A significant positive correlation between the level of Cu/Zn-SOD activity and the levels of Cu (P = 0.003) and Zn (P = 0.005) was found in the cataractous lenses. DNA sequencing revealed three intronic INDEL variations in exon4 of SOD1 gene. Splice-junction analysis showed the potential of IVS4+42delG in creating a new cryptic acceptor site. If it is involved in alternate splicing, it could result in generation of SOD1 mRNA transcripts lacking exon4 region. Transcript analysis revealed the presence of complete SOD1 mRNA transcripts. Genotyping revealed the presence of IVS4+42delG polymorphism in all subjects. CONCLUSIONS The decrease in the activity of SOD1 isoform in cataractous lenses was associated with the decreased level of mRNA transcripts and their protein expression and was not associated with either modulation in the level of enzyme cofactors or with INDEL variations.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008345	Manganese	A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D002386	Cataract	Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)	Cataract, Membranous,Lens Opacities,Pseudoaphakia,Cataracts,Cataracts, Membranous,Lens Opacity,Membranous Cataract,Membranous Cataracts,Opacities, Lens,Opacity, Lens,Pseudoaphakias
D003067	Coenzymes	Small molecules that are required for the catalytic function of ENZYMES. Many VITAMINS are coenzymes.	Coenzyme,Enzyme Cofactor,Cofactors, Enzyme,Enzyme Cofactors,Cofactor, Enzyme
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D004252	DNA Mutational Analysis	Biochemical identification of mutational changes in a nucleotide sequence.	Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D005260	Female		Females
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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