Dopamine regulates cell cycle regulatory proteins via cAMP, Ca²⁺/PKC, MAPKs, and NF‐κB in mouse embryonic stem cells

Abstract

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-kappaB. 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-kappaB signaling pathways.

NMDA and Dopamine Converge on the NMDA-Receptor to Induce ERK Activation and Synaptic Depression in Mature Hippocampus

“…In certain conditions D2 stimulation did not activate p38 [41]. Nevertheless, it was recently shown that dopamine itself, and either D1 agonist or D2 agonist, all induce various MAPKs activation [50]. In spite of this research, coincidence detection between NMDA and dopamine signaling has not been determined in any of the MAPK family members.…”

Epidermal Growth Factor-Induced Proliferation of Chicken Primordial Germ Cells: Involvement of Calcium/Protein Kinase C and NFKB11

“…Likewise, several reports indicate that nuclear factor (NF)-KB1, a family of dimeric transcription factors that regulates cell division, apoptosis, and inflammation, could be activated through EGF or EGFR system [13][14][15]. In addition, the Ca 2þ /PKC, NFKB1 signal pathway was found to mediate DNA synthesis in mouse embryonic stem cells [16]. Furthermore, Ge et al [17] demonstrated that PKC-linked NFKB1 activation modulated ginsenoside-stimulated proliferation of chicken PGCs.…”

Dopamine Receptors in Human Embryonic Stem Cell Neurodifferentiation

“…Previous reports have shown that D1, D4, and D5 message is expressed in human neural progenitors, while human EBs, but not hESCs, have been shown to express D1 mRNA [46,47]. In addition, mouse ESCs have been shown to express D1 and D2 receptors [48]. In rat embryos, D1 and D2 receptors are found in the striatum at least by E14 [49].…”