Defective Neuropeptide Processing and Ischemic Brain Injury: A Study on Proprotein Convertase 2 and its Substrate Neuropeptide in Ischemic Brains
| Autor: | Roger P. Simon, Giuseppe Pignataro, Jing-Quan Lan, Donald F. Steiner, Xiaorong Zhu, An Zhou, Hongbo Zhao, Zhi-Gang Xiong, Aaron J White, Manabu Minami, Tao Yang, Shuqin Zhan |
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| Přispěvatelé: | Zhan, S, Zhao, H, J., White A, Minami, M, Pignataro, Giuseppe, Yang, T, Zhu, X, Lan, J, Xiong, Z, Steiner, Df, Simon, Rp, Zhou, A. |
| Rok vydání: | 2009 |
| Předmět: |
endocrine system
medicine.medical_specialty Time Factors Ischemia Proprotein convertase 2 Neuropeptide Dynorphin In situ hybridization Dynorphins Neuroprotection Article Brain ischemia Internal medicine opioid peptide neuropeptide processing medicine Animals RNA Messenger proprotein convertase 2 In Situ Hybridization business.industry Neuropeptides medicine.disease Peptide Fragments brain ischemia Rats Up-Regulation Stroke Neuropeptide processing Endocrinology Neurology Reperfusion neuroprotection Neurology (clinical) Cardiology and Cardiovascular Medicine business dynorphin |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 29:698-706 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1038/jcbfm.2008.161 |
| Popis: | Using a focal cerebral ischemia model in rats, brain ischemia-induced changes in expression levels of mRNA and protein, and activities of proprotein convertase 2 (PC2) in the cortex were examined. In situ hybridization analyses revealed a transient upregulation of the mRNA level for PC2 at an early reperfusion hour, at which the level of PC2 protein was also high as determined by immunocytochemistry and western blotting. When enzymatic activities of PC2 were analyzed using a synthetic substrate, a significant decrease was observed at early reperfusion hours at which levels of PC2 protein were still high. Also decreased at these reperfusion hours were tissue levels of dynorphin-A(1-8) (DYN-A(1-8)), a PC2 substrate, as determined by radioimmunoassay. Further examination of PC2 protein biosynthesis by metabolic labeling in cultured neuronal cells showed that in ischemic cells, the proteolytic processing of PC2 was greatly attenuated. Finally, in mice, an intracerebroventricular administration of synthetic DYN-A(1-8) significantly reduced the extent of ischemic brain injury. In mice those lack an active PC2, exacerbated brain injury was observed after an otherwise non-lethal focal ischemia. We conclude that brain ischemia attenuates PC2 and PC2-mediated neuropeptide processing. This attenuation may play a role in the pathology of ischemic brain injury. |
| Databáze: | OpenAIRE |
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