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. 2008 Feb 1;366(1):86-91.
doi: 10.1016/j.bbrc.2007.11.104. Epub 2007 Dec 3.

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain

John Anagli  1 , Kadija Abounit, Paul Stemmer, Yuxia Han, Lisa Allred, Shantel Weinsheimer, Ashkhen Movsisyan, Donald Seyfried
Affiliations

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain

John Anagli et al. Biochem Biophys Res Commun. .

Abstract

The effects of selective inhibition of cathepsins B and L on postischemic protein alterations in the brain were investigated in a rat model of middle cerebral artery occlusion (MCAO). Cathepsin B activity increased predominantly in the subcortical region of the ischemic hemisphere where the levels of collapsing mediator response protein 2, heat shock cognate 70 kDa protein, 60 kDa heat shock protein, protein disulfide isomerase A3 and albumin, were found to be significantly elevated. Postischemic treatment with Cbz-Phe-Ser(OBzl)-CHN(2), cysteine protease inhibitor 1 (CP-1), reduced infarct volume, neurological deficits and cathepsin B activity as well as the amount of heat shock proteins and albumin found in the brain. Our data strongly suggests that the decrease in heat shock protein levels and the significant reduction of serum albumin leakage into the brain following acute treatment with CP-1 is indicative of less secondary ischemic damage, which ultimately, is related to less cerebral tissue loss and improved neurological recovery of the animals.

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Figures

Fig. 1
Fig. 1
Cathepsin B activity in the right cortex (RC), right subcortex (RSC), left cortex (LC) and left subcortex (LSC) of rat brain. Activity is expressed in units of enzyme activity per mg of soluble brain protein.
Fig. 2
Fig. 2
A, ~66 kDa protein levels (shown by arrow) in RSC of ischemic CP-1 treated (681–686), stroke-control (691–696) and sham-operated (701–706) animals. B, Densitometric analysis of the ~66 kDa protein bands in RSC (n = 6).
Fig. 2
Fig. 2
A, ~66 kDa protein levels (shown by arrow) in RSC of ischemic CP-1 treated (681–686), stroke-control (691–696) and sham-operated (701–706) animals. B, Densitometric analysis of the ~66 kDa protein bands in RSC (n = 6).
Fig. 3
Fig. 3
A, Western blot analysis for CRMP2 (left panel), HSC70 (middle panel) and RSA (right panel) levels in the RSC of sham-operated (lane 1), ischemic-control (lane 2) and ischemic CP-1 treated (lane 3) rat brains. B, Densitometric analysis of immunoblots.
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