Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism

Takashi Shirakura; Feng Han; Norifumi Shiota; Shigeki Moriguchi; Jiro Kasahara; Toshiyuki Sato; Yasufumi Shirasaki; Kohji Fukunaga

doi:10.1248/bpb.28.1658

Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism

Takashi Shirakura, Feng Han, Norifumi Shiota, Shigeki Moriguchi, Jiro Kasahara, Toshiyuki Sato, Yasufumi Shirasaki, Kohji Fukunaga

PHA - Graduate School of Pharmaceutical Sciences (department affiliation only)

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Microsphere embolism (ME)-induced ischemia model in rat resembles to multiple brain embolism in human with several clinical features. We here tested whether nitric oxide (NO) production contributes to the neuronal injury in the ME model. A novel calmodulin antagonist, DY-9760e, having a potent inhibitory effect on neuronal nitric oxide synthase (nNOS), reduced brain infarct size in the ME-induced brain ischemia. Consistent with our previous observation with gerbil ischemia/reperfusion model, DY-9760e completely inhibited NO production immediately after and 24 or 48 h after ME. Unlike the gerbil ischemia/reperfusion model, protein tyrosine nitration markedly increased 6 - 48 h after ME. DY-9760e treatment completely inhibited the marked increase in the protein tyrosine nitration at 24 h after ME. These results suggest that the inhibition of NO production and protein tyrosine nitration by DY-9760e contribute to its neuroprotective action in the ME-induced brain damage.

Original language	English
Pages (from-to)	1658-1661
Number of pages	4
Journal	Biological and Pharmaceutical Bulletin
Volume	28
Issue number	9
DOIs	https://doi.org/10.1248/bpb.28.1658
Publication status	Published - 2005 Sept

Keywords

Cerebral ischemia
Dy-9760e
Microsphere
Nitric oxide
Peroxynitrite

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Shirakura, T., Han, F., Shiota, N., Moriguchi, S., Kasahara, J., Sato, T., Shirasaki, Y., & Fukunaga, K. (2005). Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism. Biological and Pharmaceutical Bulletin, 28(9), 1658-1661. https://doi.org/10.1248/bpb.28.1658

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title = "Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism",

abstract = "Microsphere embolism (ME)-induced ischemia model in rat resembles to multiple brain embolism in human with several clinical features. We here tested whether nitric oxide (NO) production contributes to the neuronal injury in the ME model. A novel calmodulin antagonist, DY-9760e, having a potent inhibitory effect on neuronal nitric oxide synthase (nNOS), reduced brain infarct size in the ME-induced brain ischemia. Consistent with our previous observation with gerbil ischemia/reperfusion model, DY-9760e completely inhibited NO production immediately after and 24 or 48 h after ME. Unlike the gerbil ischemia/reperfusion model, protein tyrosine nitration markedly increased 6 - 48 h after ME. DY-9760e treatment completely inhibited the marked increase in the protein tyrosine nitration at 24 h after ME. These results suggest that the inhibition of NO production and protein tyrosine nitration by DY-9760e contribute to its neuroprotective action in the ME-induced brain damage.",

keywords = "Cerebral ischemia, Dy-9760e, Microsphere, Nitric oxide, Peroxynitrite",

author = "Takashi Shirakura and Feng Han and Norifumi Shiota and Shigeki Moriguchi and Jiro Kasahara and Toshiyuki Sato and Yasufumi Shirasaki and Kohji Fukunaga",

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Shirakura, T, Han, F, Shiota, N, Moriguchi, S, Kasahara, J, Sato, T, Shirasaki, Y & Fukunaga, K 2005, 'Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism', Biological and Pharmaceutical Bulletin, vol. 28, no. 9, pp. 1658-1661. https://doi.org/10.1248/bpb.28.1658

Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism. / Shirakura, Takashi; Han, Feng; Shiota, Norifumi et al.
In: Biological and Pharmaceutical Bulletin, Vol. 28, No. 9, 09.2005, p. 1658-1661.

Research output: Contribution to journal › Article › peer-review

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AU - Han, Feng

AU - Shiota, Norifumi

AU - Moriguchi, Shigeki

AU - Kasahara, Jiro

AU - Sato, Toshiyuki

AU - Shirasaki, Yasufumi

AU - Fukunaga, Kohji

PY - 2005/9

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N2 - Microsphere embolism (ME)-induced ischemia model in rat resembles to multiple brain embolism in human with several clinical features. We here tested whether nitric oxide (NO) production contributes to the neuronal injury in the ME model. A novel calmodulin antagonist, DY-9760e, having a potent inhibitory effect on neuronal nitric oxide synthase (nNOS), reduced brain infarct size in the ME-induced brain ischemia. Consistent with our previous observation with gerbil ischemia/reperfusion model, DY-9760e completely inhibited NO production immediately after and 24 or 48 h after ME. Unlike the gerbil ischemia/reperfusion model, protein tyrosine nitration markedly increased 6 - 48 h after ME. DY-9760e treatment completely inhibited the marked increase in the protein tyrosine nitration at 24 h after ME. These results suggest that the inhibition of NO production and protein tyrosine nitration by DY-9760e contribute to its neuroprotective action in the ME-induced brain damage.

AB - Microsphere embolism (ME)-induced ischemia model in rat resembles to multiple brain embolism in human with several clinical features. We here tested whether nitric oxide (NO) production contributes to the neuronal injury in the ME model. A novel calmodulin antagonist, DY-9760e, having a potent inhibitory effect on neuronal nitric oxide synthase (nNOS), reduced brain infarct size in the ME-induced brain ischemia. Consistent with our previous observation with gerbil ischemia/reperfusion model, DY-9760e completely inhibited NO production immediately after and 24 or 48 h after ME. Unlike the gerbil ischemia/reperfusion model, protein tyrosine nitration markedly increased 6 - 48 h after ME. DY-9760e treatment completely inhibited the marked increase in the protein tyrosine nitration at 24 h after ME. These results suggest that the inhibition of NO production and protein tyrosine nitration by DY-9760e contribute to its neuroprotective action in the ME-induced brain damage.

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Inhibition of nitric oxide production and protein tyrosine nitration contribute to neuroprotection by a novel calmodulin antagonist, DY-9760e, in the rat microsphere embolism

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