Translationally controlled tumor protein of Brugia malayi functions as an antioxidant protein.
Translationally controlled tumor protein (TCTP) is one of the most abundantly expressed proteins in the filarial parasites as well as in the other organisms. Several functions have been suggested for TCTP family of proteins ranging from calcium binding to histamine release function. However, its physiological function is still a mystery. Previous studies showed that the expression of TCTP is increased several-fold during oxidative stress. In the present work, we report the putative antioxidant function of Brugia malayi TCTP (BmTCTP). When tested in vitro, rBmTCTP could be reduced by a variety of reducing agents including thioredoxin. Such reduced form of rBmTCTP was able to protect DNA from oxidative damage, suggesting that BmTCTP may have an antioxidant function in the parasite. Sequence analysis of filarial TCTPs revealed that there are three cysteine amino acids located in the central portion of the protein. Subsequent targeted residue modification studies showed that these cysteine residues in rBmTCTP are critical for its antioxidant function. To determine the significance of this finding, rBmTCTP was overexpressed in vivo in Escherichia coli and subjected to oxidative stress. These studies showed that rBmTCTP significantly protected cells form oxidative damage. Taken together, these findings suggest that BmTCTP might be functioning as a non-classical antioxidant protein in the filarial parasites.
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA.
Munirathinam
M
Gnanasekar
Kalyanasundaram
K
Ramaswamy
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017178:Brugia malayi / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003545:Cysteine; D053904:DNA Breaks, Single-Stranded; D018869:Heat-Shock Response; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D018384:Oxidative Stress; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1
D000975:Antioxidants; D014408:Biomarkers, Tumor; D015801:Helminth Proteins; D011994:Recombinant Proteins; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D006861:Hydrogen Peroxide; D003545:Cysteine