Abstract
We recently reported a diurnal and norepinephrine (NE) -induced expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in the rat pineal gland and postulated that this MKP-1 expression might impact adrenergic-regulated arylalkylamine-N-acetyltransferase (AA-NAT) activity via modulation of MAPKs. In this study, we investigated the effect of depletion of MKP-1 expression by using doxorubicin, a topoisomerase inhibitor that suppresses the expression of MKP-1 in other cell types and small interfering RNA targeted against Mkp1 in NE-stimulated pinealocytes. We found that both treatments were effective in inhibiting NE induction of MKP-1 expression. Moreover, both treatments also resulted in a prolonged activation of p42/44MAPK and an increase in AA-NAT induction by NE. In contrast, treatment of pinealocytes with PD98059, an inhibitor of MAPK kinase, reduced NE-stimulated AA-NAT activity. Interestingly, suppressing MKP-1 expression had no effect on the time profile of NE-stimulated p38MAPK activation. These results indicate that MKP-1 modulates the profile of AA-NAT activity by selectively shaping the activation profile of p42/44MAPK but not that of p38MAPK.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Arylalkylamine N-Acetyltransferase / biosynthesis
-
Cell Cycle Proteins / metabolism*
-
Doxorubicin / pharmacology
-
Dual Specificity Phosphatase 1
-
Enzyme Activation / drug effects
-
Enzyme Induction / drug effects
-
Flavonoids / pharmacology
-
Immediate-Early Proteins / metabolism*
-
MAP Kinase Kinase 1 / antagonists & inhibitors
-
MAP Kinase Kinase 2 / antagonists & inhibitors
-
Male
-
Mitogen-Activated Protein Kinase 1 / metabolism*
-
Mitogen-Activated Protein Kinase 3 / metabolism*
-
Norepinephrine / pharmacology
-
Phosphoprotein Phosphatases / metabolism*
-
Pineal Gland / cytology*
-
Pineal Gland / drug effects
-
Pineal Gland / enzymology*
-
Protein Phosphatase 1
-
Protein Tyrosine Phosphatases / metabolism*
-
RNA, Small Interfering / pharmacology
-
Rats
-
Rats, Sprague-Dawley
-
p38 Mitogen-Activated Protein Kinases / metabolism*
Substances
-
Cell Cycle Proteins
-
Flavonoids
-
Immediate-Early Proteins
-
RNA, Small Interfering
-
Doxorubicin
-
Arylalkylamine N-Acetyltransferase
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
p38 Mitogen-Activated Protein Kinases
-
MAP Kinase Kinase 1
-
MAP Kinase Kinase 2
-
Phosphoprotein Phosphatases
-
Protein Phosphatase 1
-
Dual Specificity Phosphatase 1
-
Dusp1 protein, rat
-
Protein Tyrosine Phosphatases
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
-
Norepinephrine