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Dopamine regulates cell cycle regulatory proteins via cAMP, Ca 2+ /PKC, MAPKs, and NF‐κB in mouse embryonic stem cells
Author(s) -
Lee Min Young,
Heo Jung Sun,
Han Ho Jae
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20674
Subject(s) - protein kinase a , chemistry , biology , microbiology and biotechnology , endocrinology , medicine , kinase
This study examined the effect of dopamine on DNA synthesis and its related signal cascades in mouse embryonic stem (ES) cells. Dopamine inhibited DNA synthesis in both a dose‐ and time‐dependent manner. Dopamine, SKF 38393 (D1 receptor agonist), and quinpirole (D2 receptor agonist) decreased the level of [ 3 H]‐thymidine incorporation. The level of cyclic adenosine 3, 5‐monophosphate (cAMP) was increased by SKF 38393 but not by quinpirole. The protein kinase C (PKC) protein was translocated from the cytosolic fraction to the membrane compartment by dopamine. Dopamine also increased [Ca 2+ ] i , which was blocked by EGTA (an extracellular Ca 2+ chelator), BAPTA‐AM (an intracellular Ca 2+ chelator), nifedipine (a L‐type Ca 2+ channel blocker), SQ 22536 [an adenylyl cyclase (AC) inhibitor] and neomycin [a phospholipase C (PLC) inhibitor]. Dopamine, SKF 38393, and quinpirole increased the level of p44/42 mitogen‐activated protein kinases (MAPKs), p38 MAPK, and stress‐activated protein kinase/Jun‐N‐terminal kinase (SAPK/JNK) phosphorylation. Dopamine also increased level of H 2 O 2 formation and activated the transcription factor family NF‐κB. Moreover, SKF 38393, quinpirole, and dopamine inhibited cell cycle regulatory proteins, which is consistent with the change in the level of [ 3 H]‐thymidine incorporation observed. The dopamine‐induced decrease in cyclin E, cyclin‐dependent protein kinase‐2 (CDK‐2), and cyclin D1, CDK‐4 were blocked by pertussis toxin (G protein inhibitor), SQ 22536, neomycin, bisindolylmaleimide I (PKC inhibitor), SB 203580 (p38 MAPK inhibitor), PD 98059 (p44/42 inhibitor), and SP 600125 (SAPK/JNK inhibitor). In conclusion, dopamine inhibits DNA synthesis in mouse ES cells via the cAMP, Ca 2+ /PKC, MAPKs, and NF‐κB signaling pathways. J. Cell. Physiol. 208: 399–406, 2006. © 2006 Wiley‐Liss, Inc.