Translationally controlled tumor protein of Brugia malayi functions as an antioxidant protein

Abstract

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.

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

“…TCTP (fortilin) has been characterized as an antiapoptotic protein (Li et al, 2001); it interacts with other antiapoptotic proteins, Mcl-1 (Zhang et al, 2002;Liu et al, 2005) and Bcl-xL . This cytoprotective role of TCTP is consistent with the recently reported antioxidant function of filarial TCTP (Gnanasekar and Ramaswamy, 2007), and with observations that TCTP levels are highly regulated in various cell-stress conditions (Schmidt et al, 2007). The importance of TCTP in preventing apoptosis in regulatory T cells and in the prevention of vascular inflammation, has recently been shown in a mouse model (Xiong et al, 2008).…”

The response profiles of HSPA12A and TCTP from Mytilus galloprovincialis to pathogen and cadmium challenge

“…As concerned to TCTP, there were few reports on TCTP expression profile of shellfish exposed to toxic metals. Recently, TCTP was reported to be an anti-apoptotic protein [38]. Hence the decrease of MgTCTP mRNA was perhaps consistent with their roles as negative regulators in apoptosis.…”

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

“…Another filarial TCTP protein (from Brugia malayi) was reported to display anti-oxidant activity. The reduced form of BmTCTP was able to protect DNA from oxidative damage (Gnanasekar and Ramaswamy 2007). Similarly, TCTP prevented hydrogen peroxide-induced cell death in murine fibroblasts (Nagano-Ito et al 2009).…”

“…They detected the parasite TCTP protein in the bloodstream of infected mice and described its histamine-releasing activity and the promotion of allergic inflammatory responses associated with filarial infections in these mice. The same group also characterised Brugia malayi TCTP as an antioxidant protein (Gnanasekar and Ramaswamy 2007) and TCTP from Schistosoma mansoni as a heat-shock protein (Gnanasekar et al 2009). Similarly, in two Trichinella species, TCTP was reported to be heat-induced (Mak et al 2001(Mak et al , 2007, indicating that it is involved in cyto-protection under heat-shock conditions.…”