1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase

Han Gil Lee, So Young Kim, Du Sik Kim, Su Ryeon Seo, Syng Ill Lee, Dong Min Shin, Patrick De Smet, Jeong Taeg Seo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effect of the potent soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) on neurite outgrowth and retraction was investigated in PC12 cells and SH-SY5Y human neuroblastoma cells. ODQ inhibited neurite outgrowth and triggered neurite retraction in the cells stimulated with nerve growth factor (NGF), staurosporine, or Y-27632. The nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO) had little effect on neurite outgrowth induced by Y-27632 or staurosporine. In the presence of ODQ, treatment of the cells with the cell-permeable cGMP analogue 8-bromo-cGMP failed to retrigger Y-27632- and staurosporine-induced neurite outgrowth. Furthermore, the depletion of sGC by RNA interference failed to prevent Y-27632- and staurosporine-induced neurite outgrowth. These results indicate that the NO/sGC/cGMP signaling cascade is not critically involved in ODQ-induced neurite remodeling. The MEK inhibitor PD98059 did not inhibit neurite outgrowth, and Y-27632 and staurosporine did not induce ERK phosphorylation, suggesting that the inhibitory effect of ODQ on neurite outgrowth is independent of the ERK signaling pathway. In contrast, pretreatment with dithionite or a hemin-glutathione mixture reversed the inhibitory effect of ODQ on Y-27632-and staurosporine-induced neurite outgrowth, indicating that ODQ might act on an intracellular redox-sensitive molecule. We conclude that ODQ inhibits Y-27632-and staurosporine-induced neurite outgrowth and triggers neurite retraction in an sGC-independent manner in neuronal cells and suggest that oxidation of unidentified redox-sensitive protein could be responsible for these effects.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalJournal of Neuroscience Research
Volume87
Issue number1
DOIs
Publication statusPublished - 2009 Mar 31

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PC12 Cells
Neurites
Staurosporine
Oxidation-Reduction
Nitric Oxide
Imidazolines
Dithionite
Soluble Guanylyl Cyclase
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
Neuronal Outgrowth
Hemin
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
Nerve Growth Factor
RNA Interference
Y 27632
Neuroblastoma
Oxides
Glutathione
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Lee, Han Gil ; Kim, So Young ; Kim, Du Sik ; Seo, Su Ryeon ; Lee, Syng Ill ; Shin, Dong Min ; De Smet, Patrick ; Seo, Jeong Taeg. / 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase. In: Journal of Neuroscience Research. 2009 ; Vol. 87, No. 1. pp. 269-277.
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abstract = "The effect of the potent soluble guanylyl cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) on neurite outgrowth and retraction was investigated in PC12 cells and SH-SY5Y human neuroblastoma cells. ODQ inhibited neurite outgrowth and triggered neurite retraction in the cells stimulated with nerve growth factor (NGF), staurosporine, or Y-27632. The nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO) had little effect on neurite outgrowth induced by Y-27632 or staurosporine. In the presence of ODQ, treatment of the cells with the cell-permeable cGMP analogue 8-bromo-cGMP failed to retrigger Y-27632- and staurosporine-induced neurite outgrowth. Furthermore, the depletion of sGC by RNA interference failed to prevent Y-27632- and staurosporine-induced neurite outgrowth. These results indicate that the NO/sGC/cGMP signaling cascade is not critically involved in ODQ-induced neurite remodeling. The MEK inhibitor PD98059 did not inhibit neurite outgrowth, and Y-27632 and staurosporine did not induce ERK phosphorylation, suggesting that the inhibitory effect of ODQ on neurite outgrowth is independent of the ERK signaling pathway. In contrast, pretreatment with dithionite or a hemin-glutathione mixture reversed the inhibitory effect of ODQ on Y-27632-and staurosporine-induced neurite outgrowth, indicating that ODQ might act on an intracellular redox-sensitive molecule. We conclude that ODQ inhibits Y-27632-and staurosporine-induced neurite outgrowth and triggers neurite retraction in an sGC-independent manner in neuronal cells and suggest that oxidation of unidentified redox-sensitive protein could be responsible for these effects.",
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1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase. / Lee, Han Gil; Kim, So Young; Kim, Du Sik; Seo, Su Ryeon; Lee, Syng Ill; Shin, Dong Min; De Smet, Patrick; Seo, Jeong Taeg.

In: Journal of Neuroscience Research, Vol. 87, No. 1, 31.03.2009, p. 269-277.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one inhibits neurite outgrowth and causes neurite retraction in PC12 cells independently of soluble guanylyl cyclase

AU - Lee, Han Gil

AU - Kim, So Young

AU - Kim, Du Sik

AU - Seo, Su Ryeon

AU - Lee, Syng Ill

AU - Shin, Dong Min

AU - De Smet, Patrick

AU - Seo, Jeong Taeg

PY - 2009/3/31

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