Decreased accumulation of beta 1-adrenergic receptor, G alpha s and total myosin heavy chain messenger RNAs in the left ventricle of senescent rat heart.
The expression of genes coding for the beta 1-adrenergic receptor (beta 1-AR), the alpha subunit of Gs and total myosin heavy chain (MHC) was compared between left ventricles (LV's) from young (6-7 weeks old) and old (22 months old) rats. The mRNA levels were quantitated by Northern or Slot blots analyses using specific DNA probes. Ageing was found to be associated with a reduction in beta 1-AR (77%), G alpha s (33%) and, total MHC (51%) mRNA levels with no concomitant change in 18S RNA and poly(A+) mRNA levels. These results indicate that transcriptional and/or post-transcriptional mechanisms participate in the control of beta-adrenergic receptor density during ageing. As in the senescent LV, beta 1-AR mRNA level is reduced in the hypertrophied LV, whereas the level of G alpha s mRNA is reduced in the senescent but not in the hypertrophied LV. From our data we conclude (1) that a dual mechanism may operate during ageing, mechanical factors indirectly regulating beta 1-AR mRNA level, while changes in G alpha s mRNA level do not depend on hemodynamic load and (2) that the re-expression of beta-MHC mRNA does not compensate for the decreased accumulation of alpha-MHC mRNA which results in a large decrease in the level of total MHC mRNA in the senescent LV.
Hardouin
S
S
INSERM U 127 Hôpital Lariboisière, Paris, France.
Bourgeois
F
F
Besse
S
S
Machida
C A
CA
Swynghedauw
B
B
Moalic
J M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015342:DNA Probes; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D006352:Heart Ventricles / Q000737:chemistry; D008297:Male; D009218:Myosins / Q000235:genetics* / Q000502:physiology; D009929:Organ Size; D012333:RNA, Messenger / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000502:physiology; D016276:Ventricular Function
D015342:DNA Probes; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D009218:Myosins