Glyceraldehyde 3-Phosphate Dehydrogenase-Telomere Association Correlates with Redox Status in Trypanosoma cruzi

Author(s)

Pariona-Llanos, Ricardo ^{[1, 2]} ; Pavani, Raphael Souza ^{[1, 2]} ; Reis, Marcelo ^{[1, 2]} ; Noel, Vincent ^{[1, 2]} ; Silber, Ariel Mariano ^[3] ; Armelin, Hugo Aguirre ^{[4, 1, 2]} ; Cano, Maria Isabel Nogueira ^[5] ; Elias, Maria Carolina ^{[1, 2]}

Affiliation

^[1] Inst Butantan, Lab Especial Ciclo Celular, Sao Paulo - Brazil

^[2] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Unit Drug Discovery, BR-05508 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo - Brazil

^[5] Univ Estadual Paulista Julio de Mesquita Filho UN, Inst Biociencias, Dept Genet, Botucatu, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 10, n. 3 MAR 16 2015.
• Web of Science Citations: 11

Abstract

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a classical metabolic enzyme involved in energy production and plays a role in additional nuclear functions, including transcriptional control, recognition of misincorporated nucleotides in DNA and maintenance of telomere structure. Here, we show that the recombinant protein T. cruzi GAPDH (rTcGAPDH) binds single-stranded telomeric DNA. We demonstrate that the binding of GAPDH to telomeric DNA correlates with the balance between oxidized and reduced forms of nicotinamide adenine dinucleotides (NAD+/NADH). We observed that GAPDH-telomere association and NAD+/NADH balance changed throughout the T. cruzi life cycle. For example, in replicative epimastigote forms of T. cruzi, which show similar intracellular concentrations of NAD+ and NADH, GAPDH binds to telomeric DNA in vivo and this binding activity is inhibited by exogenous NAD+. In contrast, in the T. cruzi non-proliferative trypomastigote forms, which show higher NAD+ concentration, GAPDH was absent from telomeres. In addition, NAD+ abolishes physical interaction between recombinant GAPDH and synthetic telomere oligonucleotide in a cell free system, mimicking exogenous NAD+ that reduces GAPDH-telomere interaction in vivo. We propose that the balance in the NAD+/NADH ratio during T. cruzi life cycle homeostatically regulates GAPDH telomere association, suggesting that in trypanosomes redox status locally modulates GAPDH association with telomeric DNA. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC