TY - JOUR
T1 - Stabilization of the B-type natriuretic peptide mRNA in cardiac myocytes by α-adrenergic receptor activation
T2 - Potential roles for protein kinase C and mitogen-activated protein kinase
AU - Hanford, Deanna S.
AU - Glembotski, Christopher C.
PY - 1996
Y1 - 1996
N2 - In cardiac myocytes, B-type natriuretic peptide (BNP) expression is induced with the rapid kinetics of a primary response gene. Like many other primary response gene transcripts, the BNP mRNA possesses destabilizing elements and is believed to be short-lived. The rapid induction of a short- lived transcript could be achieved partly by agonist-mediated increases in mRNA t( 1/4 ). Accordingly, the present study was undertaken to evaluate whether the α1-adrenergic receptor agonist, phenylephrine (PE), a known inducer of BNP expression, could stabilize the BNP mRNA and, if so, what signaling pathways might be involved. In primary myocardial cells treated with a transcription inhibitor, the t( 1/4 ) of the BNP mRNA was found to be about 1 h in the absence of PE; however, in the presence of PE, the t( 1/4 ) increased to 5 h. It was shown that neither the calmodulin kinase inhibitor, KN-62, nor the protein tyrosine kinase inhibitor, tyrphostin, blocked PE-mediated stabilization of the BNP mRNA. However, either the protein kinase C (PKC) inhibitor, GF 109203X, or the mitogen-activated protein kinase kinase (MAPKK) inhibitor, PD 098059, effected some blockade of the stabilizing effects of PE. While maximal doses of PD 098059 nearly completely blocked PE-activated MAPK, stabilization was only partially inhibited. Moreover, maximal doses of GF 109203X, which only partially blocked PE-activated MAPK, nearly completely inhibited stabilization. Thus, while MAPK appears to be required for maximal agonist-mediated stabilization, PKC seems to play a dominant role, participating through both MAPK-dependent and -independent pathways. These results establish roles for both the PKC and MAPK families in α1-adrenergic receptor-mediated stabilization of the BNP mRNA, suggesting that the rapid induction of BNP expression might be due, in part, to this agonist-mediated increase in mRNA t( 1/4 ).
AB - In cardiac myocytes, B-type natriuretic peptide (BNP) expression is induced with the rapid kinetics of a primary response gene. Like many other primary response gene transcripts, the BNP mRNA possesses destabilizing elements and is believed to be short-lived. The rapid induction of a short- lived transcript could be achieved partly by agonist-mediated increases in mRNA t( 1/4 ). Accordingly, the present study was undertaken to evaluate whether the α1-adrenergic receptor agonist, phenylephrine (PE), a known inducer of BNP expression, could stabilize the BNP mRNA and, if so, what signaling pathways might be involved. In primary myocardial cells treated with a transcription inhibitor, the t( 1/4 ) of the BNP mRNA was found to be about 1 h in the absence of PE; however, in the presence of PE, the t( 1/4 ) increased to 5 h. It was shown that neither the calmodulin kinase inhibitor, KN-62, nor the protein tyrosine kinase inhibitor, tyrphostin, blocked PE-mediated stabilization of the BNP mRNA. However, either the protein kinase C (PKC) inhibitor, GF 109203X, or the mitogen-activated protein kinase kinase (MAPKK) inhibitor, PD 098059, effected some blockade of the stabilizing effects of PE. While maximal doses of PD 098059 nearly completely blocked PE-activated MAPK, stabilization was only partially inhibited. Moreover, maximal doses of GF 109203X, which only partially blocked PE-activated MAPK, nearly completely inhibited stabilization. Thus, while MAPK appears to be required for maximal agonist-mediated stabilization, PKC seems to play a dominant role, participating through both MAPK-dependent and -independent pathways. These results establish roles for both the PKC and MAPK families in α1-adrenergic receptor-mediated stabilization of the BNP mRNA, suggesting that the rapid induction of BNP expression might be due, in part, to this agonist-mediated increase in mRNA t( 1/4 ).
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U2 - 10.1210/me.10.12.1719
DO - 10.1210/me.10.12.1719
M3 - Article
C2 - 8961280
AN - SCOPUS:0029962514
SN - 0888-8809
VL - 10
SP - 1719
EP - 1727
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 12
ER -