RAPID TRANSCRIPTIONAL ACTIVATION AND EARLY MESSENGER-RNA TURNOVER OF BRAIN NATRIURETIC PEPTIDE IN CARDIOCYTE HYPERTROPHY - EVIDENCE FOR BRAIN NATRIURETIC PEPTIDE AS AN EMERGENCY CARDIAC HORMONE AGAINST VENTRICULAR OVERLOAD
RAPID TRANSCRIPTIONAL ACTIVATION AND EARLY MESSENGER-RNA TURNOVER OF BRAIN NATRIURETIC PEPTIDE IN CARDIOCYTE HYPERTROPHY - EVIDENCE FOR BRAIN NATRIURETIC PEPTIDE AS AN EMERGENCY CARDIAC HORMONE AGAINST VENTRICULAR OVERLOAD
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DOI：
10.1172/jci118162
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发表时间：
1995-09-01
影响因子：
15.9
通讯作者：
NAKAO, K
中科院分区：
文献类型：
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作者：
NAKAGAWA, O;OGAWA, Y;NAKAO, K
脑钠肽（BNP）是一种主要在心室产生的心脏激素，而心房钠肽（ANP）的主要产生部位是心房。为了评估BNP在心室超负荷中的病理生理作用，我们用培养的新生大鼠心室心肌细胞检测了BNP和ANP在心肌肥大模型中的基因表达。在内皮素-1、苯肾上腺素或PMA诱导的心肌细胞肥大过程中，BNP mRNA的稳态水平与c-fos基因表达的“立即早期”诱导一样迅速增加，转录抑制剂放线菌素D（Actinomycin D）可完全抑制该反应，而放线菌酮（放线菌酮）的翻译阻断剂则不能抑制该反应。相反，ANP mRNA在刺激后3 h开始增加，并在心肌细胞肥大过程中积累，心室肌细胞分泌BNP的速度也比ANP更快。BNP mRNA的周转明显快于ANP mRNA，这与BNP mRNA 3 ′-非翻译区存在AUUUA突变相一致。这些结果表明BNP和ANP的基因表达在转录和转录后水平上受到不同的调控，表明BNP基因表达的特征适合于其作为抗心室超负荷的“紧急"心脏激素的可能作用。
We previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. To assess the pathophysiological role of BNP in ventricular overload, we have examined the gene expression of BNP, in comparison with that of ANP, in a model of cardiac hypertrophy using cultured neonatal rat ventricular cardiocytes, During cardiocyte hypertrophy evoked by endothelin-1, phenylephrine, or PMA, the steady state level of BNP mRNA increased as rapidly as the ''immediate-early'' induction of the c-fos gene expression, and reached a maximal level within 1 h, Actinomycin D, a transcriptional inhibitor, completely diminished the response, while the translational blockade with cycloheximide did not inhibit it, In contrast, ANP mRNA began to increase 3 h after the stimulation, and accumulated during cardiocyte hypertrophy, The BNP secretion from ventricular cardiocytes was also stimulated more rapidly than the ANP secretion, Furthermore, the turnover of BNP mRNA was significantly faster than that of ANP mRNA, being consistent with the existence of AUUUA moth in the 3'-untranslated region of BNP mRNA, These results demonstrate that the gene expression of BNP is distinctly regulated from that of ANP at transcriptional and posttranscriptional levels, and indicate that the characteristics of the BNP gene expression are suitable for its possible role as an ''emergency'' cardiac hormone against ventricular overload.