title: Streptozotocin induces neurite outgrowth via PI3K-Akt and glycogen synthase kinase 3β in Neuro2a cells.
abstract: Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various kinds of cells such as insulin-producing beta cells. However, the beneficial effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has been unknown. In this study, we examined the effect of STZ on neurite outgrowth in mouse neuronal Neuro2a cells. STZ (0.01 mM~5 mM) exerted remarkable neurite outgrowth-inducing activity in Neuro2a cells in a concentration dependent manner. STZ also had the same neurite outgrowth-inducing activity as that of retinoic acid (RA), which is well known neurite outgrowth inducer. As with the result of RA treatment, STZ administration increased MAP2-positive cells. The MAP2-positive cells reflect neurite outgrowth-induced cells. STZ (0.01 mM~5 mM) did not induce cell death, but significantly decreased cell proliferation. The serine/threonine kinase Akt, a downstream target of phosphatidylinositol-3 kinase (PI3K), was transiently phosphorylated at Ser473 and at Thr303 by STZ (5 mM) administration. Glycogen synthase kinase 3β (GSK3β), which has been reported to be inactivated by Akt, was also transiently phosphorylated at Ser9 by STZ (5 mM) administration. In addition, a blocker of PI3K, LY294002 (10 μM), significantly attenuated STZ-induced neurite outgrowth. These results suggest that STZ induces neurite outgrowth via activation of PI3K-Akt signaling pathway and GSK3β inhibition.
authors.affiliation: Department of Immunology, Kawasaki Medical School, Okayama, 701-0192, Japan. t-nishi12@med.kawasaki-m.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Nishimoto
authors.affiliation: Arts and Sciences, Faculty of Engineering, Tokyo University of Science, Yamaguchi, 756-0884, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Kimura
authors.affiliation: Faculty of Life and Medical Sciences, Doshisha University, Kyoto, 610-0394, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Nervous Disease Research Center, Graduate School of Brain Science, Doshisha University, Kyoto, 610-0394, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D002867:Chromones; D000071679:Glycogen Synthase Kinase 3 beta; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D013311:Streptozocin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one