Discoordinate regulation of contractile protein gene expression in the senescent rat myocardium.
The myocardium is a highly adaptive tissue, as evidenced by phenotypic alterations throughout development and under conditions of altered hemodynamic load. With pressure overload, the myocardium displays adult-to-fetal transitions in expression of contractile and non-contractile proteins. Most intriguing is the fact that many of these transitions are also observed in the senescent heart. The purpose of this work was to establish if the thin filament regulatory proteins, troponin I and troponin T, exhibit reexpression of early developmental isoforms, suggestive of coordinate reprogramming of contractile protein isoform expression. As a functional index of reexpression of the early isoform of troponin I, slow skeletal troponin I, myofibrils were isolated from 12 and 24-month-old Fischer 344 rat ventricles and assayed for myofibrillar ATPase activity at pH 7.0 and 6.5. Both preparations displayed rightward shifts in Ca-ATPase relationships with no differences between groups. SDS-PAGE and Western blot analysis showed that whereas myosin heavy chain expression underwent a transition to predominance of the early development isoform, beta-myosin heavy chain, there was no reexpression of the fetal isoforms of either troponin I or troponin T in the rat heart at 24 months of age. Northern blot analysis using cDNA probes specific for cardiac or slow skeletal troponin I also confirmed the lack of slow skeletal reexpression in the 24-month ventricle. These results are significant in that they demonstrate a lack of coordinate expression of contractile protein isoforms under myocardial adaptation to the aging process.
Ball
K L
KL
Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60680.
Solaro
R J
RJ
D000251:Adenosine Triphosphatases / Q000032:analysis; D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003285:Contractile Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D009218:Myosins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D014336:Troponin / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D019210:Troponin I; D020107:Troponin T
D003285:Contractile Proteins; D012333:RNA, Messenger; D014336:Troponin; D019210:Troponin I; D020107:Troponin T; D004247:DNA; D000251:Adenosine Triphosphatases; D009218:Myosins