New inhibitors of calpain prevent degradation of cytoskeletal and myelin proteins in spinal cord in vitro

New inhibitors of calpain prevent degradation of cytoskeletal and myelin proteins in spinal cord... We have determined the effects of the calpain inhibitors AK275 and AK295 upon purified m‐calpain and calcium‐mediated degradation of neurofilament protein (NFP) in rat spinal cord in vitro. After incubation, the soluble radioactivity and/or extent of myelin basic protein (MBP) or NFP degradation was determined. Fifty percent of caseinolytic activity was inhibited by both inhibitors at 0.6 μM concentration, while more than 90% inhibition was seen at 1.6 μM. In contrast, 37% and 64% inhibition of MBP degradation was seen with AK295 and AK275, respectively, at 10 μM concentration. The extent of NFP degradation in spinal cord was quantified from immunoblot enhanced chemiluminescence. The calcium‐mediated breakdown of NFP was inhibited by both AK275 and AK295, and the inhibition was dose‐dependent. A 50% inhibition of NFP degradation was seen with AK295 at 10 μM and was almost completely inhibited at 25–50 μM. AK295 was slightly more potent than AK275. These studies suggest that these potent calpain inhibitors may be used therapeutically to provide neuroprotection in vivo in experimental central nervous system trauma and ischemia. J. Neurosci. Res. 51:218–222, 1998. © 1998 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

New inhibitors of calpain prevent degradation of cytoskeletal and myelin proteins in spinal cord in vitro

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Publisher
Wiley
Copyright
Copyright © 1998 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
D.O.I.
10.1002/(SICI)1097-4547(19980115)51:2<218::AID-JNR10>3.0.CO;2-4
Publisher site
See Article on Publisher Site

Abstract

We have determined the effects of the calpain inhibitors AK275 and AK295 upon purified m‐calpain and calcium‐mediated degradation of neurofilament protein (NFP) in rat spinal cord in vitro. After incubation, the soluble radioactivity and/or extent of myelin basic protein (MBP) or NFP degradation was determined. Fifty percent of caseinolytic activity was inhibited by both inhibitors at 0.6 μM concentration, while more than 90% inhibition was seen at 1.6 μM. In contrast, 37% and 64% inhibition of MBP degradation was seen with AK295 and AK275, respectively, at 10 μM concentration. The extent of NFP degradation in spinal cord was quantified from immunoblot enhanced chemiluminescence. The calcium‐mediated breakdown of NFP was inhibited by both AK275 and AK295, and the inhibition was dose‐dependent. A 50% inhibition of NFP degradation was seen with AK295 at 10 μM and was almost completely inhibited at 25–50 μM. AK295 was slightly more potent than AK275. These studies suggest that these potent calpain inhibitors may be used therapeutically to provide neuroprotection in vivo in experimental central nervous system trauma and ischemia. J. Neurosci. Res. 51:218–222, 1998. © 1998 Wiley‐Liss, Inc.

Journal

Journal of Neuroscience ResearchWiley

Published: Jan 15, 1998

References

  • Increased calpain activity and expression in spinal cord injury
    Banik, Banik; Lobo, Lobo; Gantt‐Wilford, Gantt‐Wilford; Hogan, Hogan

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