DIFFERENTIAL REGULATION BY TUMOR-NECROSIS-FACTOR-ALPHA OF BETA(1)-ADRENORECEPTOR, BETA(2)-ADRENORECEPTOR, AND BETA(3)-ADRENORECEPTOR GENE-EXPRESSION IN 3T3-F442A ADIPOCYTES
K. Elhadri et al., DIFFERENTIAL REGULATION BY TUMOR-NECROSIS-FACTOR-ALPHA OF BETA(1)-ADRENORECEPTOR, BETA(2)-ADRENORECEPTOR, AND BETA(3)-ADRENORECEPTOR GENE-EXPRESSION IN 3T3-F442A ADIPOCYTES, The Journal of biological chemistry, 272(39), 1997, pp. 24514-24521
Modulation of beta-adrenoreceptor expression by tumor necrosis factor-
alpha (TNF-alpha) was investigated in murine 3T3-F442A adipocytes. TNF
-alpha treatment of mature adipocytes decreased beta(3)-adrenoreceptor
mRNA content in a time-and concentration-dependent manner, with a 8.5
-fold decrease observed after a 6-h exposure to 300 pM TNF-alpha. beta
(1)-Adrenoreceptor mRNA abundance was slightly decreased by TNF-alpha
treatment, while beta(2)-adrenoreceptor mRNA levels were potently indu
ced (6-fold increase at 6 h), (-)-[I-125]Iodocyanopindolol saturation
and competition binding experiments indicated that TNF-alpha induced a
2-fold decrease in beta(3)-adrenoreceptor number, a nonsignificant re
duction in beta(1)-subtype population, and a similar to 4.5-fold incre
ase in beta(2)-adrenoreceptor density, This correlated with a lower EC
value measured for epinephrine in stimulating adenylyl cyclase, where
as the EC50 value for norepinephrine increased. Nuclear run-on assays
on isolated nuclei and mRNA stability measurements showed that TNF-alp
ha increased both beta(2)-adrenoreceptor gene transcription and beta(2
)-adrenoreceptor mRNA half-life, while beta(1)- and beta(3)-adrenorece
ptor gene expression was modulated only at the transcriptional level b
y the cytokine. These findings demonstrate a differential modulation b
y TNF-alpha of the three beta-adrenoreceptor subtypes in adipocytes, w
hich may contribute to metabolic disorders induced by the cytokine in
the adipocyte.