In this study, we demonstrated that the T. cruzi cds TcCOX10 and TcCOX15 code for HOS and HAS enzymes that are functionally active in yeast cells. Mitochondrial targeting sequences are highly conserved through evolution, and even though the sequences reported for trypanosomatids are shorter
than the ones in other cells, including yeast (Hausler et al., 1997), our results showed that the T. cruzi sequences for Cox10 and Cox15 were recognized by the yeast mitochondrial importing machinery. These sequences were imported and properly folded to produce active enzymes in the yeast mitochondria. The observed changes in the mRNA levels of TcCOX10 and TcCOX15 could be a form of regulation reflecting differences in respiratory requirements at different life stages. In order to test these hypotheses and to address how T. cruzi transports heme into the mitochondrion, we are working to expand our studies on this system. We are grateful www.selleckchem.com/products/Adriamycin.html to Prof.
Dennis Winge and Eric L. Hegg for the yeast plasmids and strains. This study was supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). J.A.C. is a member of the carrier of scientific investigator of CONICET (Argentina). A.M.S. and B.A.S.M. are indebted to Fundacão de Amparo à Pesquisa do Estado de São Paulo (FAPESP, project #08-57596-4) and to CNPq (Project #473906/2008-2). A.M.S. is a fellow from CNPq and a member of the Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas, INBEQMeDI (Brazil). Appendix S1. The Trypanosoma selleckchem cruzi proteins TcCox10 and TcCox15 catalyze the formation of heme A in the yeast Saccharomyces cerevisiae Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials
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“Dinh et al. have reported that, in a single centre, eight of 115 HIV-infected patients (6.9%) had unexplained noncirrhotic portal hypertension (NCPH) . Their report provides further evidence that NCPH in HIV-positive patients is a vascular disease of the liver. It also highlights the potential severity of the syndrome and underlines how important it is to develop early screening strategies. Dr Dinh’s Dichloromethane dehalogenase group is the tenth team worldwide to report cases of NCPH in HIV-positive patients. Undoubtedly, NCPH is an emerging disease in HIV-infected patients. Our group currently follows 21 similar patients. All were referred to our unit for unexplained abnormal liver function tests with or without portal hypertension. As did Dr Dinh, we found that the Fibroscan® was inappropriate to diagnose NCPH in HIV-positive patients. The median Fibroscan® value in our cohort was 8.3 kPa [interquartile range (IQR) 6.6–9.4 kPa] and there was no correlation between Fibroscan® values and the severity of the disease.