Transcriptional regulation of α 1-adrenoceptor gene in the rat liver during different phases of sepsis

Abstract

Changes in α 1-adrenoceptor (α 1AR) gene expression in the rat liver during different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hyperglycemic phase (9 h after CLP, early sepsis) followed by a hypoglycemic phase (18 h after CLP; late sepsis). The [ 3H]prazosin binding studies show that the density of α 1AR was increased by 30% during the early phase while it was decreased by 24% during the late phase of sepsis. Western blot analyses reveal that α 1AR protein level was elevated by 48% during early sepsis but was decreased by 55% during late sepsis. Northern blot analyses depict that the steady-state level of α 1bAR mRNA was enhanced by 21% during the early phase but was declined by 29% during the late phase of sepsis. Nuclear run-off assays show that the transcription rate of α 1bAR gene transcript was increased by 76% during early sepsis while it was decreased by 29% during late sepsis. The actinomycin D pulse-chase studies indicate that the half-life of α 1bAR mRNA remained unaffected during the early and the late phases of sepsis. These findings demonstrate that during the early phase of sepsis, the increase in the rate of transcription of α 1bAR gene paralleled with the elevations in the α 1bAR mRNA abundance and α 1AR protein level, while during the late phase of sepsis, the decrease in the rate of transcription of α 1bAR gene coincided with the declines in the α 1bAR mRNA abundance and the α 1AR protein level in the rat liver. These observations indicate that the altered expression of α 1AR genes in the rat liver during the progression of sepsis was regulated transcriptionally.