CD38/cADPR/Ca2+ pathway promotes cell proliferation and delays nerve growth factor-induced differentiation in PC12 cells.
Intracellular Ca(2+) mobilization plays an important role in a wide variety of cellular processes, and multiple second messengers are responsible for mediating intracellular Ca(2+) changes. Here we explored the role of one endogenous Ca(2+)-mobilizing nucleotide, cyclic adenosine diphosphoribose (cADPR), in the proliferation and differentiation of neurosecretory PC12 cells. We found that cADPR induced Ca(2+) release in PC12 cells and that CD38 is the main ADP-ribosyl cyclase responsible for the acetylcholine (ACh)-induced cADPR production in PC12 cells. In addition, the CD38/cADPR signaling pathway is shown to be required for the ACh-induced Ca(2+) increase and cell proliferation. Inhibition of the pathway, on the other hand, accelerated nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells. Conversely, overexpression of CD38 increased cell proliferation but delayed NGF-induced differentiation. Our data indicate that cADPR plays a dichotomic role in regulating proliferation and neuronal differentiation of PC12 cells.
Yue
Jianbo
J
Department of Physiology, The University of Hong Kong, Hong Kong. jyue@hku.hk
Wei
Wenjie
W
Lam
Connie M C
CM
Zhao
Yong-Juan
YJ
Dong
Min
M
Zhang
Liang-Ren
LR
Zhang
Li-He
LH
Lee
Hon-Cheung
HC
D036541:ADP-ribosyl Cyclase / Q000096:biosynthesis / Q000235:genetics; D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis* / Q000235:genetics; D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D018678:Cholinergic Agents / Q000378:metabolism / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D018678:Cholinergic Agents; D008562:Membrane Glycoproteins; D036563:Cyclic ADP-Ribose; D020932:Nerve Growth Factor; D036541:ADP-ribosyl Cyclase; C498156:Cd38 protein, rat; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine; D002118:Calcium
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