Mitochondrial transcription factor A is increased but expression of ATP synthase beta subunit and medium-chain acyl-CoA dehydrogenase genes are decreased in hearts of copper-deficient rats.
The mechanism(s) by which impaired mitochondrial respiratory function and the accumulation of lipid droplets and mitochondria in hearts of copper-deficient rats occur remains unclear. It is not known whether specific components of the regulatory pathway involved in mitochondrial biogenesis, such as mitochondrial transcription factor A (mtTFA) and nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2), are activated in copper deficiency. Little is known about gene expression of enzymes involved in fatty acid oxidation (FAO) in hearts of copper-deficient rats. Male weanling rats were fed copper-adequate (CuA), copper-deficient (CuD) or pair-fed (CuP) diets for 5 wk. Mitochondria and lipid droplet volume densities from electron micrographs were greater and there was an elevation in the mtTFA protein level in hearts of copper-deficient rats. DNA binding activities of NRF-1 and NRF-2 did not differ among the groups. Northern blot analysis of cardiac tissue revealed that transcripts of F(1)F(0)-ATP synthase subunit c were greater, but mRNA levels of ATP synthase beta subunit and the FAO enzyme, medium-chain acyl-CoA dehydrogenase (MCAD), were lower in hearts of copper-deficient rats. Long-chain acyl-CoA dehydrogenase (LCAD) mRNA levels did not differ among treatment groups. These results suggest that certain components of the mitochondrial biogenesis program are activated in hearts of copper-deficient rats. F(1)F(0)-ATP synthase beta subunit and MCAD transcript levels remain low, which may contribute to impaired mitochondrial respiratory function, decreased fatty acid utilization and lipid droplet accumulation in hearts of copper-deficient rats.
Mao
S
S
Department of Human Nutrition and Food Management, The Ohio State University, Columbus, OH 43210, USA.
Leone
T C
TC
Kelly
D P
DP
Medeiros
D M
DM
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*; D004032:Diet; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D015534:Trans-Activators; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics; D015854:Up-Regulation; D029867:Xenopus Proteins
D012333:RNA, Messenger; C489030:Tfam protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; C097078:XL-MTTFA protein, Xenopus; D029867:Xenopus Proteins; D003300:Copper; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D006180:Proton-Translocating ATPases