Prolonged calpain activation is widely recognized as a key component of neurodegeneration in a variety of pathological conditions. Numerous reports have also indicated that synaptic activation of NMDA receptors (NMDARs) provides neuroprotection against a variety of insults. Here, we report the paradoxical finding that such neuroprotection involves calpain activation. NMDAR activation in culture...

Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. We identified two different missense mutations in the CAPN5 gene in three ADNIV kindreds. CAPN5 encodes calpain-5, a calcium-activated cysteine protease t...

The inhibitory domains of calpastatin contain three highly conserved regions, A, B, and C, of which A and C bind calpain in a strictly Ca(2+)-dependent manner but have no inhibitory activity whereas region B inhibits calpain on its own. We synthesized the 19-mer oligopeptides corresponding to regions A and C of human calpastatin domain I and tested their effect on human erythrocyte mu-calpain a...

Inhibitors of calpains, calcium-activated neutral proteases, protect against cell death produced by anoxia and a variety of toxicants both in vitro and in vivo. The problems with known calpain inhibitors are a lack of specificity, low membrane permeability, and/or low potency. The goal of this study was to determine the effects of seven novel dipeptide and tripeptide calpain inhibitors on calpa...

Properties of the calpain bound to myofibrils in longissimus muscle from callipyge or noncallipyge sheep were examined after 0, 1, 3, and 10 d of postmortem storage at 4 degrees C. Western analysis has shown that most of this calpain is mu-calpain, although the sensitivity of the antibodies used in the earlier studies could not eliminate the possibility that up to 10% of the calpain was m-calpa...

The effects of bovine skeletal muscle m-calpain and calpastatin on the degradation of casein and isolated bovine myofibrils were characterized under various pH values (7.0, 6.2, 5.7) and ionic strengths (32 to 400 mM KCl) at 25 degrees C. Caseinolytic assays indicated that m-calpain activity increased with increasing pH (P < .01) but decreased with increasing ionic strength (P < .01). Regardles...

Recent studies in septic models have shown that myocardial calpain activity and TNF-α expression increase during sepsis and that inhibition of calpain activation downregulates myocardial TNF-α expression and improves cardiac dysfunction. However, the mechanism underlying this pathological process is unclear. Thus, in the present study, we aimed to explore whether IκBα/NF-κB signaling linked myo...

It is generally accepted that the Ca(2+)-dependent interaction of calpain with calpastatin is the most relevant mechanism involved in the regulation of Ca(2+)-induced proteolysis. We now report that a calpain-calpastatin association can occur also in the absence of Ca(2+) or at very low Ca(2+) concentrations, reflecting the physiological conditions under which calpain retains its inactive confo...

Aging is associated with abnormalities in kidney function, but the exact mechanisms are unknown. We examined calpains 1, 2, and 10 protein levels in kidneys from rats, mice, and humans of various ages and determined whether calpain 10 is required for cell viability. Calpain 10 protein expression decreased in the kidney, but not in the liver, of aging Fischer 344 rats, and this decrease was atte...

PC12 cells are a nerve growth factor-responsive clone derived from a rat pheochromocytoma. Treatment with nerve growth factor causes the cells to differentiate. One of the hallmarks of this differentiation is the generation of neurites. PC12 cells contain both calpain I and calpain II; about 90% of the total calpain activity is due to calpain II. Treatment of the cells with nerve growth factor ...