Secretin induces neurite outgrowth of PC12 through cAMP-mitogen-activated protein kinase pathway.
The gastrointestinal functions of secretin have been fairly well established. However, its function and mode of action within the nervous system remain largely unclear. To gain insight into this area, we have attempted to determine the effects of secretin on neuronal differentiation. Here, we report that secretin induces the generation of neurite outgrowth in pheochromocytoma PC12 cells. The expressions of Tau and beta-tubulin, neuronal differentiation markers, are increased upon secretin stimulation. In addition, secretin induces sustained mitogen-activated protein kinase (MAPK) activation and also stimulates the cAMP secretion. Moreover, the neurite outgrowth elicited by secretin is suppressed to a marked degree in the presence of either PD98059, a specific MAPK/ERK kinase (MEK) inhibitor, or H89, a specific protein kinase A (PKA) inhibitor. Taken together, these observations demonstrate that secretin induces neurite outgrowth of PC12 cells through cAMP- MAPK pathway, and provide a novel insight into the manner in which secretin participates in neuritogenesis.
Kim
Hyeon Soo
HS
Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.
Yumkham
Sanatombi
S
Kim
Sun-Hee
SH
Yea
Kyungmoo
K
Shin
You Chan
YC
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D015151:Immunoblotting; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012633:Secretin / Q000494:pharmacology*
D005456:Fluorescent Dyes; D012633:Secretin; D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate