Gene expression analysis in mitochondria from chagasic mice: alterations in specific metabolic pathways.
Cardiac hypertrophy and remodelling in chagasic disease might be associated with mitochondrial dysfunction. In the present study, we characterized the cardiac metabolic responses to Trypanosoma cruzi infection and progressive disease severity using a custom-designed mitoarray (mitochondrial function-related gene array). Mitoarrays consisting of known, well-characterized mitochondrial function-related cDNAs were hybridized with 32P-labelled cDNA probes generated from the myocardium of mice during immediate early, acute and chronic phases of infection and disease development. The mitoarray successfully identified novel aspects of the T. cruzi-induced alterations in the expression of the genes related to mitochondrial function and biogenesis that were further confirmed by real-time reverse transcriptase-PCRs. Of note is the up-regulation of transcripts essential for fatty acid metabolism associated with repression of the mRNAs for pyruvate dehydrogenase complex in infected hearts. We observed no statistically significant changes in mRNAs for the enzymes of tricarboxylic acid cycle. These results suggest that fatty acid metabolism compensates the pyruvate dehydrogenase complex deficiencies for the supply of acetyl-CoA for a tricarboxylic acid cycle, and chagasic hearts may not be limited in reduced energy (NADH and FADH2). The observation of a decrease in mRNA level for several subunits of the respiratory chain complexes by mitoarray as well as global genome analysis suggests a limitation in mitochondrial oxidative phosphorylation-mediated ATP-generation capacity as the probable basis for cardiac homoeostasis in chagasic disease.
Garg
Nisha
N
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA. nigarg@utmb.edu
Gerstner
Arpad
A
Bhatia
Vandanajay
V
DeFord
James
J
Papaconstantinou
John
J
D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000201:enzymology* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics; D005796:Genes / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics*; D032448:Myoblasts, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000469:parasitology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014349:Trypanosoma cruzi / Q000469:parasitology