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Appearance of Nuclear-sorted Caspase-12 Fragments in Cerebral Cortical and Hippocampal Neurons in Rats Damaged by Autologous Blood Clot Embolic Brain Infarctions

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Abstract

Following endoplasmic reticulum (ER) stress, cerebral infarctions have been reported to involve an apoptotic process, including the activation of the caspase cascade. To confirm whether fragmented caspase-12, which is activated by cleavage and is detectable during ER stress, is also involved in embolic cerebral infarctions in rats, we adopted an autologous blood clot model for the analysis of cerebral infarctions. We performed experiments in rats with brain infarctions, which are closely related to embolic cerebral infarctions. We utilized a homologous blood clot, i.e., natural materials, to form the infarct area. Our findings reveal that caspase-12 is fragmented when infarct areas form in cerebral cortical neurons. Interestingly, we observed that these fragments translocated to the nuclei of not only cerebral cortical neurons but hippocampal neurons. We further found that glucose-regulated protein 78 (GRP78), a marker of ER stress, is up-regulated in both cerebral cortical and hippocampal neurons during cerebral infarction. This result suggests that the fragmentation of caspase-12 and the subsequent nuclear translocation of these fragments are involved in the brain infarction process in rats.

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Abbreviations

ER:

Endoplasmic reticulum

GRP78:

Glucose-regulated protein 78

Bcl-2:

B cell/lymphoma-2

MCAO:

Middle cerebral artery occlusion

HE:

Hematoxylin and eosin

TUNEL:

Terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end labeling

UPR:

Unfolded protein response

PBS:

Phosphate-buffered saline

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Acknowledgments

This study was supported by grants-in-aid for scientific research (KAKENHI 21570152) and the “Strategic Project to Support the Formation of Research Bases at Private Universities (SENRYAKU)” (2008–2012) from MEXT (Ministry of Education, Culture, Sports, Science and Technology of Japan). This work was also supported by the Kansai University Special Research Fund, 2009.

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Authors and Affiliations

  1. Laboratory of Neurobiology, Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka, 564-8680, Japan

    Koji Shimoke, Kensuke Sugihara, Masamichi Nobuhara, Hiroki Maruoka & Toshihiko Ikeuchi

  2. Department of Pathology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Yoshinori Matsuki & Motoshige Kudo

  3. Department of Pathology, Mitsui Memorial Hospital, 1 Izumi-cho, Kanda, Chiyoda-ku, Tokyo, 101-8643, Japan

    Yoshinori Matsuki

  4. Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate-cho, Suita, Osaka, 564-8680, Japan

    Kenji Fukunaga & Yoshinobu Matsumura

  5. Division of Differentiation and Development, Department of Inherited Metabolic Disorders, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-machi, Kodaira, Tokyo, 187-8502, Japan

    Eriko Fujita

  6. Technology Research Laboratory, KURABO, Neyagawa, Osaka, 572-0823, Japan

    Hiroki Maruoka

Authors
  1. Koji Shimoke
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  2. Yoshinori Matsuki
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  3. Kenji Fukunaga
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  4. Yoshinobu Matsumura
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  5. Eriko Fujita
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  6. Kensuke Sugihara
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  7. Masamichi Nobuhara
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  9. Toshihiko Ikeuchi
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  10. Motoshige Kudo
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Corresponding author

Correspondence to Koji Shimoke.

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Shimoke, K., Matsuki, Y., Fukunaga, K. et al. Appearance of Nuclear-sorted Caspase-12 Fragments in Cerebral Cortical and Hippocampal Neurons in Rats Damaged by Autologous Blood Clot Embolic Brain Infarctions. Cell Mol Neurobiol 31, 795–802 (2011). https://doi.org/10.1007/s10571-011-9687-0

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  • DOI: https://doi.org/10.1007/s10571-011-9687-0

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