Trypanosoma cruzi ?High Mobility Group B? protein: what we know about its nuclear and extracellular functions.

TAVERNELLI, LUIS; PERDOMO, VIRGINIA; MANARIN, ROMINA; SERRA, ESTEBAN; CRIBB, PAMELA

Rosario

Congreso; 50th Annual Meeting SAIB; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

High Mobility Group Box (HMGB) proteins are evolutionary-conserved components of chromatin. They act as architectural factors taking part of important nuclear processes like transcriptional regulation, DNA repair and replication. Beyond these intranuclear functions, some HMGBs can be secreted by certain cells and play important roles as inflammatory mediators. The HMGB protein from Trypanosoma cruzi (TcHMGB) has two HMG box domains and a 110 N-terminal domain unique of kinetoplastid HMGBs. It is a nuclear protein expressed in all life cycle stages and shows architectural properties. The specific N-terminal domain seems to have an additional DNA binding site and a putative nuclear localization signal. We found that TcHMGB can also be secreted, and protein acetylation seems to enhance this process. To test if TcHMGB can act as an immune regulator, we stimulated RAW 264.7 macrophages with recombinant TcHMGB for different time periods. Culture supernatants were collected and nitric oxide production was analyzed measuring nitrite release by Griess reaction. Also, total RNA was purified from treated macrophages and mRNAs for different cytokines were quantified by qRT-PCR. Recombinant TcHMGB showed to be able of inducing macrophage activation in vitro. These preliminary results indicate that TcHMGB may have both nuclear functions and a role in inflammation.