Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia

Motohiro Morioka; Takayuki Kawano; Shigetoshi Yano; Yutaka Kai; Hiromasa Tsuiki; Yutaka Yoshinaga; Jun Matsumoto; Tatsumi Maeda; Jun ichiro Hamada; Hideyuki Yamamoto; Kohji Fukunaga; Jun ichi Kuratsu

doi:10.1016/j.bbrc.2006.06.096

Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia

Motohiro Morioka, Takayuki Kawano, Shigetoshi Yano, Yutaka Kai, Hiromasa Tsuiki, Yutaka Yoshinaga, Jun Matsumoto, Tatsumi Maeda, Jun ichiro Hamada, Hideyuki Yamamoto, Kohji Fukunaga, Jun ichi Kuratsu

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Abstract

We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.

Original language	English
Pages (from-to)	273-278
Number of pages	6
Journal	Biochemical and biophysical research communications
Volume	347
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2006.06.096
Publication status	Published - 2006 Aug 18
Externally published	Yes

Keywords

Hippocampus
Ischemia
Phosphorylation
Tau factor

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2006.06.096

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Morioka, M., Kawano, T., Yano, S., Kai, Y., Tsuiki, H., Yoshinaga, Y., Matsumoto, J., Maeda, T., Hamada, J. I., Yamamoto, H., Fukunaga, K., & Kuratsu, J. I. (2006). Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia. Biochemical and biophysical research communications, 347(1), 273-278. https://doi.org/10.1016/j.bbrc.2006.06.096

Morioka, M, Kawano, T, Yano, S, Kai, Y, Tsuiki, H, Yoshinaga, Y, Matsumoto, J, Maeda, T, Hamada, JI, Yamamoto, H, Fukunaga, K & Kuratsu, JI 2006, 'Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia', Biochemical and biophysical research communications, vol. 347, no. 1, pp. 273-278. https://doi.org/10.1016/j.bbrc.2006.06.096

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title = "Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia",

abstract = "We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.",

keywords = "Hippocampus, Ischemia, Phosphorylation, Tau factor",

author = "Motohiro Morioka and Takayuki Kawano and Shigetoshi Yano and Yutaka Kai and Hiromasa Tsuiki and Yutaka Yoshinaga and Jun Matsumoto and Tatsumi Maeda and Hamada, {Jun ichiro} and Hideyuki Yamamoto and Kohji Fukunaga and Kuratsu, {Jun ichi}",

note = "Funding Information: This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Science and Culture of Japan.",

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doi = "10.1016/j.bbrc.2006.06.096",

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T1 - Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia

AU - Morioka, Motohiro

AU - Kawano, Takayuki

AU - Yano, Shigetoshi

AU - Kai, Yutaka

AU - Tsuiki, Hiromasa

AU - Yoshinaga, Yutaka

AU - Matsumoto, Jun

AU - Maeda, Tatsumi

AU - Hamada, Jun ichiro

AU - Yamamoto, Hideyuki

AU - Fukunaga, Kohji

AU - Kuratsu, Jun ichi

N1 - Funding Information: This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Science and Culture of Japan.

PY - 2006/8/18

Y1 - 2006/8/18

N2 - We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.

AB - We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.

KW - Hippocampus

KW - Ischemia

KW - Phosphorylation

KW - Tau factor

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Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia

Abstract

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