期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 43, 期 1, 页码 98-107出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2009.10.001
关键词
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资金
- National Institutes of Health [R01DA04271, R01NS24553, R01MH077305]
- NIH Neurosciences Microscopy [P30NS047101]
- NIH NRSA [F30DA023292]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH077305] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS024553, P30NS047101] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [F30DA023292, R01DA004271] Funding Source: NIH RePORTER
Dynorphin opioid neuropeptides mediate neurotransmission for analgesia and behavioral functions. Dynorphin A, dynorphin B, and alpha-neoendorphin are generated from prodynorphin by proteolytic processing. This study demonstrates the significant role of the cysteine protease cathepsin L for producing dynorphins. Cathepsin L knockout mouse brains showed extensive decreases in dynorphin A, dynorphin B, and alpha-neoendorphin that were reduced by 75%, 83%, and 90%, respectively, compared to controls. Moreover, cathepsin L in brain cortical neurons was colocalized with dynorphins in secretory vesicles, the primary site of neuropeptide production. Cellular coexpression of cathepsin L with prodynorphin in PC12 cells resulted in increased production of dynorphins A and B. Comparative studies of PC1/3 and PC2 convertases showed that PC1/3 knockout mouse brains had a modest decrease in dynorphin A, and PC2 knockout mice showed a minor decrease in alpha-neoendorphin. Overall, these results demonstrate a prominent role for cathepsin L, jointly with PC1/3 and PC2, for production of dynorphins in brain. (C) 2009 Published by Elsevier Inc.
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