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Cathepsin B and Phospo-JNK in Relation to Ongoing Apoptosis after Transient Focal Cerebral Ischemia in the Rat

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Abstract

Cathepsin B, one of major lysosomal cathepsins, and JNK, a downstream component of Rho kinase (ROCK), are two families of proteases, which play an important role in ischemic cell apoptosis. However, the interrelationship between Cathepsin B and JNK in apotosis has not been examined. In the present study, rats were decapitated at 0, 2, 6, 24, 48 h of reperfusion after 2 h of middle cerebral artery occlusion (MCAO); TUNEL-positive cells appeared in the ipsilateral preoptic region during reperfusion after 2-h MCAO, and gradually increased to a peak of 24 h after reperfusion; Phospho-JNK (p-JNK) immunoreactivity, occurring after Cathepsin B expression, was gradually increased and peaked altogether with Cathepsin B at 6-h reperfusion; Fasudil (5 mg/kg, intraperitoneally), an inhibitor of ROCK, decreased the level of p-JNK and apoptotic neurons, and had no effect on cathepsin B; Immunofluorescent double labeling showed that the colocalization of cathepsin B with p-JNK appeared in the preoptic region at 2, 6, 24, 48 h of reperfusion. These findings indicate that a signal transduction pathway by ischemia–reperfusion is most likely to exist: lysosomal cathepsin B-Rho/Rho kinase pathway-JNK signaling pathway-mitochondrial-dependent intrinsic pathway.

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Acknowledgments

This study was subsidized by University of South China, the First Hospital of Changsha and Changsha Institute of Neurology. We would like to extend our great gratitude to teaches from Neurology Lab of Xiangya Hospital of Central South University for their help.

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Authors and Affiliations

  1. Department of Neurology, the First Hospital of Changsha, Changsha, Hunan, 410005, China

    Zhi Bo Zhang

  2. Department of Neurology, the First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi, 341000, China

    Zhi Gang Li

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  1. Zhi Bo Zhang
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  2. Zhi Gang Li
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Correspondence to Zhi Gang Li.

Additional information

Z. G. Li and Z. B. Zhang contributed equally to this work.

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Zhang, Z.B., Li, Z.G. Cathepsin B and Phospo-JNK in Relation to Ongoing Apoptosis after Transient Focal Cerebral Ischemia in the Rat. Neurochem Res 37, 948–957 (2012). https://doi.org/10.1007/s11064-011-0687-8

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  • DOI: https://doi.org/10.1007/s11064-011-0687-8

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