Does strong hypertrophic condition induce fast mitochondrial DNA mutation of rabbit heart?
Homo- and heteroplasmic mitochondrial DNA (mtDNA) mutations were observed and identified in an isoproterenol-induced rabbit model of cardiac hypertrophy. Genes encoding proteins essential for catalyzing mitochondrial electron transfer and for generating the proton motive force, such as NADH dehydrogenases (ND2, ND3, ND4, and ND6), cytochrome b, and ATPase 8, showed increased susceptibility for mutation. Specifically, five mutations caused amino acid changes and were located in Complex I and Complex V gene clusters. To our knowledge, this is the first demonstration of a relationship between cardiac hypertrophy induced by a strong sympathetic load and rapid mtDNA mutations.
Kim
Taeho
T
Department of Physiology and Biophysics, School of Medicine, Inje University, Busan 614-735, Republic of Korea.
Thu
Vu Thi
VT
Han
Il-Yong
IY
Youm
Jae Boum
JB
Kim
Euiyong
E
Kang
Sun Woo
SW
Kim
Yang Wook
YW
Lee
Jae Hwa
JH
Joo
Hyun
H
D019943:Amino Acid Substitution; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000235:genetics*; D045303:Cytochromes b / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009245:NADH Dehydrogenase / Q000145:classification / Q000235:genetics; D017354:Point Mutation; D011817:Rabbits; D013997:Time Factors
D004272:DNA, Mitochondrial; D045303:Cytochromes b; D009245:NADH Dehydrogenase; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; D007545:Isoproterenol