Microtubules are involved in early hypertrophic responses of myocardium during pressure overload.
Mechanical overloading to cardiac muscle causes fetal contractile protein gene expression and acceleration of protein synthesis. Myocyte microtubules might be involved in these pressure overload-induced hypertrophic responses. We assessed c-fos and fetal contractile protein genes such as beta-myosin heavy chain (MHC) and alpha-skeletal actin using Northern blot analysis and quantified total cardiac protein, DNA, and RNA content in the left ventricular myocardium obtained from four groups of rats: sham-operated rats; sham-operated rats treated with colchicine, which depolymerized microtubules; rats in which acute pressure overload was imposed by abdominal aortic constriction for 3 days (AoC); and AoC rats treated with colchicine (AoC + colchicine). Systolic arterial pressure was elevated to a similar degree in AoC and AoC + colchicine rats. c-fos and beta-MHC mRNA levels were significantly upregulated in AoC rats, which was attenuated by microtubule inhibition. Both RNA content and RNA-to-DNA ratio, the index of the protein synthesis capacity, were increased in AoC rats, which effect was also abolished by colchicine. Furthermore, induction of nonfunctioning microtubules by taxol or deuterium oxide exerted the same inhibitory effects. Thus the hypertrophic responses of the myocardium during pressure overload might depend on the integrity of myocyte microtubules.
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka 812-82, Japan.
M
M
Takahashi
H
H
Tsutsui
H
H
Tagawa
K
K
Igarashi-Saito
K
K
Imanaka-Yoshida
A
A
Takeshita
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D003078:Colchicine / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016762:Genes, fos; D006321:Heart / Q000502:physiology / Q000503:physiopathology*; D006352:Heart Ventricles; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013599:Systole; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D011506:Proteins; D014404:Tubulin; D012313:RNA; D004247:DNA; D018995:Myosin Heavy Chains; D003078:Colchicine