Antithetical accumulation of myosin heavy chain but not alpha-actin mRNA isoforms during early stages of pressure-overload-induced rat cardiac hypertrophy.
Myocardial response to a hemodynamic overload involves changes in the expression of isogenes encoding myosin heavy chain (MHC) and actin: beta-MHC/alpha-MHC and skeletal/cardiac alpha-actin mRNA isoform ratios are increased. It is not known whether these changes are due to increased accumulations of the two neosynthesized transcripts, beta-MHC and skeletal alpha-actin, or whether the mRNA isoforms normally present, alpha-MHC and cardiac alpha-actin, are concomitantly decreased. To answer these questions, using dot-blot hybridizations, primer extension, and exonuclease VII mapping assays, we have analyzed the content of sarcomeric MHC and actin mRNAs in the poly(A+) RNA in left ventricles of 23-24-day-old rats 18 and 24 hours after a pressure overload induced by stenosis of the thoracic aorta. The results showed a 1.9-fold increase in poly(A+) RNA after the stenosis. Skeletal/cardiac alpha-actin mRNA isoforms were already increased fivefold (from 0.19 to 0.99) at 18 hours, and this was exclusively due to a 5.5-fold increase in skeletal alpha-actin mRNA. At 24 hours, this ratio was increased ninefold (from 0.14 to 1.22), and this was due to a 4.3-fold increase in the level of skeletal alpha-actin mRNAs (p < 0.001) and a 1.9-fold decrease of cardiac alpha-actin mRNA (p < 0.001), restoring the same proportion of sarcomeric actin mRNA in sham-operated and operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Chassagne
C
C
INSERM U 127, Hôpital Lariboisière, Paris, France.
Wisnewsky
C
C
Schwartz
K
K
D000199:Actins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000502:physiology*; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D007536:Isomerism; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000737:chemistry / Q000235:genetics*; D015345:Oligonucleotide Probes / Q000235:genetics; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012518:Sarcomeres / Q000378:metabolism; D014158:Transcription, Genetic
D000199:Actins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D009218:Myosins