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CD38/cADPR/Ca2+ pathway promotes cell proliferation and delays nerve growth factor-induced differentiation in PC12 cells.


ABSTRACT: 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.

SUBMITTER: Yue J 

PROVIDER: S-EPMC2785564 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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CD38/cADPR/Ca2+ pathway promotes cell proliferation and delays nerve growth factor-induced differentiation in PC12 cells.

Yue Jianbo J   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  

The Journal of biological chemistry 20090820 43


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  ...[more]

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