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Neural Thrombin and Protease Nexin I Kinetics After Murine Peripheral Nerve Injury
Author(s) -
Smirnova Irina V.,
Ma Jianxin Y.,
Citron Bruce A.,
Ratzlaff Keith T.,
Gregory Eugene J.,
Akaaboune Mohammed,
Festoff Barry W.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67052188.x
Subject(s) - sciatic nerve , thrombin , sciatic nerve injury , nerve injury , serine protease , chemistry , proteases , peripheral nerve injury , serpin , crush injury , protease , endocrinology , medicine , biochemistry , anesthesia , enzyme , surgery , platelet , gene
We addressed the balance between thrombin and its serpin protease nexin I (PNI) after sciatic nerve injury in the mouse. Prothrombin levels increased twofold 24 h after nerve crush, as measured by a specific chromogenic assay, and peaked at day 3. Thrombin activity also increased 2–4 days after injury in distal sciatic nerve segments. Nerve RNA analysis using reverse transcriptase‐polymerase chain reaction (RT‐PCR) assay confirmed that prothrombin was synthesized locally. We also monitored PNI levels in these injured nerve samples by complex formation with an 125 I‐labeled target protease and found peak activity occurring later, 6–9 days after the thrombin induction. These data indicate that nerve injury first induces the synthesis of prothrombin, which is subsequently converted to active thrombin. Nerve crush‐induced thrombin is followed by the generation of functionally active PNI and may be directly responsible for its induction. By immunocytochemistry with anti‐PNI antibody, we found that activated Schwann cells were the source of induced PNI. These results support the concept that the balance between serine proteases and their serpins is dysregulated during nerve injury and suggests a role for its reestablishment in nerve damage repair.