Recombinant human mitochondrial transcription factor A stimulates mitochondrial biogenesis and ATP synthesis, improves motor function after MPTP, reduces oxidative stress and increases survival after endotoxin.
Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive manner. SH-SY5Y cells showed rhTFAM concentration-dependent reduction of methylpyridinium (MPP(+))-induced oxidative stress and increases in lowered ATP levels and viability. Mice treated with weekly i.v. rhTFAM showed increased mitochondrial gene copy number, complex I protein levels and ATP production rates; oxidative damage to proteins was decreased ~50%. rhTFAM treatment improved motor recovery rate after treatment with MPTP and dose-dependently improved survival in the lipopolysaccharide model of endotoxin sepsis.
Thomas
Ravindar R
RR
Morris Udall Parkinson's Disease Research Center of Excellence, University of Virginia, Charlottesville, VA, United States.
Khan
Shaharyar M
SM
Portell
Francisco R
FR
Smigrodzki
Rafal M
RM
Bennett
James P
JP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019446:Endotoxemia / Q000188:drug therapy / Q000401:mortality*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D000255:Adenosine Triphosphate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine