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Volume 17, Number 21, Issue of November 1, 1997 pp. 8156-8168
Copyright ©1997 Society for Neuroscience

Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury

Received June 10, 1997; revised Aug. 7, 1997; accepted Aug. 15, 1997.

Isobel A. Scarisbrick^{1, 2}, Melvin D. Towner¹, and Paul J. Isackson¹

¹ Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida 32224, and ² Molecular Neuroscience Research, Mayo Clinic Rochester, Rochester, Minnesota 55905

A full-length cDNA clone of a previously unidentified serine protease, myelencephalon-specific protease (MSP), has been isolated by using a PCR cloning strategy and has been shown to be expressed in a nervous system and spinal cord-specific pattern. Sequence analysis demonstrated that MSP is most similar in sequence to neuropsin, trypsin, and tissue kallikrein and is predicted to have trypsin-like substrate specificity. MSP mRNA was found to be ~10-fold greater in the CNS of the rat and human, as compared with most peripheral tissues, and within the CNS was found to be highest by a factor of four in the medulla oblongata and spinal cord. Levels of mRNA encoding tissue plasminogen activator (tPA) also were elevated in the spinal cord but were more widespread in peripheral tissues as compared with MSP.

In the adult rat lumbosacral spinal cord, in situ localization of MSP mRNA demonstrated 2-fold higher levels in the white, as compared with the gray, matter. MSP mRNA expression was shown to increase 3-fold in the white matter and 1.5-fold in the gray laminae at 72 hr after intraperitoneal injection of the AMPA/kainate glutamate receptor-specific agonist, kainic acid (KA). MSP mRNA remained elevated in the ventral gray matter, including expression associated with the motor neurons of lamina IX, at 7 d after the initial excitotoxic insult. Together, these observations indicate that MSP is in a position to play a fundamental role in normal homeostasis and in the response of the spinal cord to injury.

Key words: serine protease; spinal cord; brain stem; medulla oblongata; motor neuron; oligodendrocyte; CNS; excitotoxicity; kainic acid

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