Calpain: new perspectives in molecular diversity and physiological‐pathological involvement

Saido, Takaomi C.; Sorimachi, Hiroyuki; Suzuki, Koichi

doi:10.1096/fasebj.8.11.8070630

Cited by 642 publications

(455 citation statements)

References 5 publications

Supporting

Mentioning

436

Contrasting

Unclassified

Order By: Relevance

“…Investigation of the production of specific breakdown products (FBDP) of substrates specific to calpain proteolysis has proved useful in detecting calpain activity in nervous and sensory tissues (Siman et al, 1984;Saido et al, 1993Saido et al, , 1994Blomgren et al, 1995;Shields et al, 1999;Rajgopal and Vemuri, 2002;Ladrech et al, 2004 among others). Among these substrates, fodrin, the neuronal form of spectrin, is a specific actin cross-linking protein that is cleaved by calpain to a greater extent than other substrates.…”

Section: Hal Author Manuscript Inserm-00145385 Versionmentioning

confidence: 99%

A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma

et al. 2007

View full text Add to dashboard Cite

Free radical and calcium buffering mechanisms are implicated in cochlear cell damage that has been induced by sound trauma. Thus in this study we evalua ted the therapeutic effect of a novel dual inhibitor of calpains and of lipid peroxidation (BN 82270) on the permanent hearing and hair cell loss induced by sound trauma.Perfusion of BN 82270 into the scala tympani of the guinea pig cochlea prevented the formation of calpain-cleaved fodrin, translocation of cytochrome c, DNA fragmentation and hair cell degeneration caused by sound trauma. This was confirmed by functional tests in vivo, showing a clear dose-dependent reduction of permanent hearing loss (ED 50 = 4.07 µM) with almost complete protection at 100 µM.Furthermore, BN82270 still remained effective even when applied onto the round window membrane after sound trauma had occurred, within a therapeutic window of 24hours. This indicates that BN 82270 may be of potential therapeutic value in treating the cochlea after sound trauma.

show abstract

Section: Hal Author Manuscript Inserm-00145385 Versionmentioning

confidence: 99%

A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma

et al. 2007

View full text Add to dashboard Cite

show abstract

“…It has been shown that calcium overload leads to neurodegeneration in cerebral ischemia (Choi, 1995). Excessive calcium levels are responsible for activation of intracellular calcium proteases, such as calpains, which play a pivotal role in cytoskeletal degeneration and ischemic cell death (Saido et al, 1994;Wang and Yuen, 1994). Calpain is a cysteine protease which is overactivated in several pathological conditions, including all forms of excitotoxicity (Azuma et al, 1991;Siman and Noszek, 1988;Wang and Yuen, 1994).…”

Section: Introductionmentioning

confidence: 99%

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

Montero

Poulsen

Noraberg

et al. 2007

Experimental Neurology

View full text Add to dashboard Cite

In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-D-aspartate (NMDA) excitotoxicity. Hippocampal slice cultures were pretreated for 24 h with 100 IU/ml EPO (= 26 nM) or 26 nM CEPO before OGD or NMDA lesioning. Exposure to EPO and CEPO continued during OGD and for the next 24 h until histology, as well as during the 24 h exposure to NMDA. Neuronal cell death was quantified by cellular uptake of propidium iodide (PI), recorded before the start of OGD and NMDA exposure and 24 h after. In cultures exposed to OGD or NMDA, CEPO reduced PI uptake by 49 ± 3 or 35 ± 8%, respectively, compared to lesion-only controls. EPO reduced PI uptake by 33 ± 5 and 15 ± 8%, respectively, in the OGD and NMDA exposed cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of α-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least as efficient neuroprotectant as EPO when excitotoxicity is modeled in mouse hippocampal slice cultures.

show abstract

“…The two major calpain isozymes, m-calpain (calpain I, m-CANP) and m-calpain (calpain II, m-CANP) require approximately 10 75 and 10 73 M Ca 2+ , respectively, for activity in vitro (Saido et al, 1994;Suzuki et al, 1992). There are other calpain gene family members which are distributed in speci®c tissues (Suzuki et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the growth of WI-38 fibroblasts by benzyloxycarbonyl-Leu-Leu-Tyr diazomethyl ketone: evidence that cleavage of p53 by a calpain-like protease is necessary for G1 to S-phase transition

et al. 1997

View full text Add to dashboard Cite

The e ect of a calpain-selective cell permeant inhibitor, benzyloxycarbonyl Leu-Leu-Tyr diazomethylketone (ZLLY-CHN 2 ), on the serum-stimulated growth of WI-38 human ®broblasts has been investigated. Only cell permeant protease inhibitors with activity against calpains prevented progression into S-phase. Protein blotting experiments indicated that p53 immunoreactivity increased in late G 1 cells treated with ZLLY-CHN 2 . The content of p21 Waf1/Cip1 CDK inhibitor also increased, providing a mechanism for the observed failure to enter S-phase. Further studies indicated that p53 could be degraded by a ZLLY-CHN 2 -sensitive protease immediately prior to S-phase, but that proteolysis did not occur after this critical time point. Chelation of extracellular Ca 2+ by addition of EGTA inhibited the p53 degradation. Consistent with proteolysis of p53 in late G 1 phase, m-calpain immunoreactivity transiently accumulated in cell nuclei at this time. ZLLY-CHN 2 did not appear to increase p53 mRNA in WI-38 cells. Puri®ed mcalpain required only 1 to 3 mM Ca 2+ to proteolyze p53 in WI-38 cell lysates. These results indicate that ZLLY-CHN 2 inhibits progression of WI-38 cells into S-phase by inactivating a calpain-like protease that is responsible for proteolysis of constitutively expressed p53 in late G 1 .

show abstract

Calpain: new perspectives in molecular diversity and physiological‐pathological involvement

Cited by 642 publications

References 5 publications

A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma

A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

Inhibition of the growth of WI-38 fibroblasts by benzyloxycarbonyl-Leu-Leu-Tyr diazomethyl ketone: evidence that cleavage of p53 by a calpain-like protease is necessary for G1 to S-phase transition

Contact Info

Product

Resources

About