Trypanosoma cruzi, causative agent of Chagas disease (CD), remains a public health problem in Latin America and is emerging in non-endemic areas. Phospholipids (PL) are essential components of biomemb Show more
Trypanosoma cruzi, causative agent of Chagas disease (CD), remains a public health problem in Latin America and is emerging in non-endemic areas. Phospholipids (PL) are essential components of biomembranes and their enzymatic modification by phospholipases yields bioactive lipids that modulate immune responses. Anti-PL antibodies have been associated with autoimmune diseases and inflammation, potentially influencing CD pathology by recognising PL and PL-binding proteins. T. cruzi Phospholipase A1 (TcPLA1) hydrolyses membrane PL and participates in parasite-host cell interactions. This study evaluated IgM and IgG antibody responses against phosphatidylcholine, phosphatidylethanolamine, and their derived lysophospholipids (LPL), as well as recombinant TcPLA1, during experimental T. cruzi infection with two strains: RA (high virulence) and K98 (low virulence). It also aimed to predict the recognition capacity of TcPLA1 by CD patients using in silico analysis. Antibody responses were analysed by enzyme-linked immunosorbent assay (ELISA) using different PL and recombinant TcPLA1 as antigens. Lytic activity assays were performed to evaluate the functional impact of anti-PL antibodies. The CHAGASTOPE resource was used to predict TcPLA1 antigenicity. This study identified IgM and IgG antibodies against PL, LPL and TcPLA1 during experimental T. cruzi infection. Different amino acid sequences of TcPLA1 showed stronger antigenic recognition by CD patient's sera. The presence of these antibodies suggests their involvement in the pathogenesis of CD and their potential as markers for disease monitoring and prognosis. Show less
Phytofluene is a colorless carotenoid with potential health benefits that displays a higher bioavailability compared to carotenoids such as lutein, β-carotene or lycopene. Several studies suggest its Show more
Phytofluene is a colorless carotenoid with potential health benefits that displays a higher bioavailability compared to carotenoids such as lutein, β-carotene or lycopene. Several studies suggest its bioavailability displays an elevated interindividual variability. The aim of this work is to investigate whether a combination of SNPs is associated with this variability. Thirty-seven healthy adult males consume a test meal that provides phytofluene from a tomato puree. Phytofluene concentrations are measured at fast and in chylomicrons at regular time intervals after meal intake. Identification of the combination of SNPs that best explained the interindividual variability of the phytofluene response is assessed by partial least squares regression. There is a large interindividual variability in the phytofluene response, with CV = 88%. Phytofluene bioavailability is positively correlated with fasting plasma phytofluene concentration (r = 0.57; p = 2 × 10 This study reports a combination of SNPs that is associated with a significant part of the interindividual variability of phytofluene bioavailability in a healthy male adult population. Show less
Members of the poly-ADP-ribose polymerase (PARP) family catalyse the ADP-ribosylation of target proteins and are known to play important roles in many cellular processes, including DNA repair, differe Show more
Members of the poly-ADP-ribose polymerase (PARP) family catalyse the ADP-ribosylation of target proteins and are known to play important roles in many cellular processes, including DNA repair, differentiation and transcription. The majority of PARPs exhibit mono-ADP-ribosyltransferase activity rather than PARP activity; however, little is known about their biological activity. In the present study, we report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly-ADP-ribose polymerase (TIPARP), mono-ADP-ribosylates and positively regulates liver X receptor α (LXRα) and LXRβ activity. Overexpression of TIPARP enhanced LXR-reporter gene activity. TIPARP knockdown or deletion reduced LXR regulated target gene expression levels in HepG2 cells and in Tiparp(-/-)mouse embryonic fibroblasts (MEFs) respectively. Deletion and mutagenesis studies showed that TIPARP's zinc-finger and catalytic domains were required to enhance LXR activity. Protein interaction studies using TIPARP and LXRα/β peptide arrays revealed that LXRs interacted with an N-terminal sequence (a.a. 209-236) of TIPARP, which also overlapped with a putative co-activator domain of TIPARP (a.a. 200-225). Immunofluorescence studies showed that TIPARP and LXRα or LXRβ co-localized in the nucleus.In vitroribosylation assays provided evidence that TIPARP mono-ADP-ribosylated both LXRα and LXRβ. Co-immunoprecipitation (co-IP) studies revealed that ADP-ribosylase macrodomain 1 (MACROD1), but not MACROD2, interacted with LXRs in a TIPARP-dependent manner. This was complemented by reporter gene studies showing that MACROD1, but not MACROD2, prevented the TIPARP-dependent increase in LXR activity. GW3965-dependent increases in hepatic Srebp1 mRNA and protein expression levels were reduced in Tiparp(-/-)mice compared with Tiparp(+/+)mice. Taken together, these data identify a new mechanism of LXR regulation that involves TIPARP, ADP-ribosylation and MACROD1. Show less