Neurotropin ® inhibits calpain activity upregulated by specific alternation of rhythm in temperature in the mesencephalon of rats

Fujisawa, Hiroki; Numazawa, Takumi; Kawamura, Minoru; Naiki, Mitsuru

doi:10.1016/j.lfs.2016.12.018

Cited by 3 publications

(2 citation statements)

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“…The present data report that estimated calpain activity by evaluating the protein level of α II-spectrin breakdown product (150 kDa) using Western blotting. 28 , 29 In this study, we used the percentage of α II-spectrin breakdown product in the total of α II-spectrin to estimate calpain activity. The full-length α II-spectrin and α II-spectrin breakdown product protein expression were present in the dorsal root of vehicle and RTX groups (n = 8, Figure 1(b) ).…”

Section: Resultsmentioning

confidence: 99%

“… 31 Calpain cleaves α II-spectrin to generate α II-spectrin breakdown products (145 kDa and 150 kDa) 32 and the calpain activity can be estimated by evaluating the protein level of α II-spectrin breakdown product (150 kDa) using Western blotting. 29 , 33 Recent studies have shown that TRPV1 activation induces an increase in intracellular calcium, activates Ca 2+ -activated calpain, and eventually leads cell injury in diabetic DRG neurons. 11 , 12 Furthermore, RTX may excite TRPV1 receptors and their downstream signaling components Ca 2+ /calmodulin independent protein kinase and Akt, thus enhance calpain expression and activation in dorsal root of RTX-induced PHN model.…”

Section: Discussionmentioning

confidence: 99%

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Activation and expression of μ-calpain in dorsal root contributes to RTX-induced mechanical allodynia

Yuan

Gao

et al. 2017

Mol Pain

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BackgroundCalpain is a calcium-dependent cysteine protease, and inhibition of calpain by pre-treatment with MDL28170 attenuated the rat mechanical allodynia in a variety of pain models. Postherpetic neuralgia (Shingles) is a neuropathic pain conditioned with the presence of profound mechanical allodynia. Systemic injection of resiniferatoxin can reproduce the clinical symptoms of postherpetic neuralgia. In this study, we determined to study whether activation of calpain contributes to cleave the myelin basic protein of dorsal root and is involved in resiniferatoxin-induced mechanical allodynia of postherpetic neuralgia animal model.ResultsResiniferatoxin up-regulated the expression and activation of µ-calpain in dorsal root. The expression of µ-calpain was located in Schwann cell of dorsal root, and resiniferatoxin increased the expression of µ-calpain in Schwann cell in L4–L6 dorsal root at six weeks after injection. Resiniferatoxin also induced myelin basic protein degradation in L4–L6 dorsal root at six weeks after injection. Moreover, intraperitoneal injection of calpain inhibitor MDL28170 prevented the degradation of myelin basic protein and then reduced the sprouting of myelinated afferent fibers into spinal lamina II, thus relieving resiniferatoxin-induced mechanical allodynia.ConclusionsUp-regulation and activation of µ-calpain located in Schwann cell may be the mechanism underlying resiniferatoxin-mediated proteolysis of myelin basic protein in dorsal root. Calpain inhibitor MDL28170 prevents resiniferatoxin-induced sprouting of myelinated afferent fibers and mechanical allodynia through inhibition of degradation of the myelin basic protein in dorsal root. Our results indicate that inhibition of pathological µ-calpain activation may present an interesting novel drug target in the treatment of postherpetic neuralgia.

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Section: Resultsmentioning

confidence: 99%