J. Yang et al., Transcriptional and posttranscriptional regulation of beta(2)-adrenergic receptor gene in rat liver during sepsis, AM J P-REG, 46(1), 1999, pp. R132-R139
Citations number
43
Categorie Soggetti
Physiology
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Changes in beta(2)-adrenergic receptor (beta(2)-AR) gene expression in the
rat liver during different phases of sepsis were studied. Sepsis was induce
d by cecal ligation and puncture (CLP). Septic rats exhibit two metabolical
ly distinct phases: an initial hyperglycemic (9 h after CLP; early sepsis)
followed by a hypoglycemic phase (18 h after CLP; late sepsis). The [H-3]di
hydroalprenolol binding studies show that the density of beta(2)-AR was dec
reased by 12 and 35% during the early and late phases of sepsis, respective
ly. Western blot analyses depict that the beta(2)-AR protein level was redu
ced by 37 and 72% during early and late sepsis, respectively. The reverse t
ranscription polymerase chain reaction and Southern blot analyses reveal th
at the steady-state level of beta(2)-AR mRNA was decreased by 37% during ea
rly phase and 77% during late phase of sepsis. Nuclear run-off assays show
that the rate of transcription of beta(2)-AR mRNA was reduced by 36% during
early sepsis and 64% during late sepsis. The stability assays indicate tha
t the half-life of beta(2)-AR mRNA was shortened by 21 and 50% during the e
arly and late phases of sepsis, respectively, indicating that the rate of d
egradation of beta(2)-AR mRNA was progressively enhanced during sepsis. The
se findings demonstrate that the beta(2)-AR gene was underexpressed in the
liver during the progression of sepsis, and, furthermore, the underexpressi
on of the beta(2)-AR gene was the result of a reduction in the rate of tran
scription coupled with an enhancement in the rate of degradation of beta(2)
-AR gene transcripts. Thus our findings that the transcriptional and posttr
anscriptional regulation of beta(2)-AR gene associated with decreases in be
ta(2)-AR number and its protein expression may provide a molecular mechanis
tic explanation for the development of hypoglycemia during the late stage o
f sepsis.