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Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity.

Up-regulation of the persistent sodium current (INaP) and down-regulation of the potassium/chloride extruder KCC2 lead to spasticity after spinal cord injury (SCI). We here identified calpain as the driver of the up- and down-regulation of INaP and KCC2, respectively, in neonatal rat lumbar motoneurons. Few days after SCI, neonatal rats developed behavioral signs of spasticity with the emergence of both hyperreflexia and abnormal involuntary muscle contractions on hindlimbs. At the same time, in vitro isolated lumbar spinal cords became hyperreflexive and displayed numerous spontaneous motor o…

Принимающая ячейка Calpains может отвести структурные протеины от полипротеина Enterovirus.

Enteroviruses — это небольшие RNA вирусы, которые вызывают болезни с различными симптомами — от легкого до острого. Enterovirus белки транслируются как единый полипротеин, который изливается вирусными протезами для высвобождения капсида и неструктурных белков. Здесь мы показываем, что также клеточные кальпаины могут играть роль в обработке энтеровирального полипротеина. Используя очищенные кальпаины 1 и 2 в ходе анализа in vitro, мы показываем, что добавление кальпаинов приводит к увеличению выбросов VP1 и VP3 капсидовых белков из P1 видов энтеровируса B, обнаруженных в результате западного пя

Совпадение в аннотации оригинала
Enteroviruses are small RNA viruses that cause diseases with various symptoms ranging from mild to severe. Enterovirus proteins are translated as a single polyprotein, which is cleaved by viral proteases to release capsid and nonstructural proteins. Here, we show that also cellular calpains have a potential role in the processing of the enteroviral polyprote…

The Abnormal Architecture of Healed Diabetic Ulcers Is the Result of FAK Degradation by Calpain 1.

Delayed wound healing is a major complication of diabetes occurring in approximately 15% of chronic diabetic patients. It not only significa … nder a high glucose condition both in vitro and in vivo. This is secondary to increased activity of calpain 1, the primary enzyme responsible for focal adhesion kinase degradation, which becomes induced in hyperglycemia. We demonstrate that selective inhibition of calpain 1 activation improves wound healing and normalizes the mechanical properties of diab …

Delivery of Topically Applied Calpain Inhibitory Peptide to the Posterior Segment of the Rat Eye.

We developed an inhibitory peptide that specifically acts against mitochondrial μ-calpain (Tat-μCL, 23 amino acid, 2857.37 Da) and protects photoreceptors in retinal dystrophic rats. In the present study, we topically administered Tat-μCL to the eyes of Sprague-Dawley rats for 7 days to determine both the delivery route of the peptide to the posterior segment of the eye and the kinetics after topical application in adult rats. Distribution of the peptide was determined by immunohistochemical analysis, and enzyme-linked immune-absorbent assay was used to quantify the accumulation in the retina.…

The calpain inhibitor MDL28170 induces the expression of apoptotic markers in Leishmania amazonensis promastigotes.

BACKGROUND: Human cutaneous leishmaniasis is caused by distinct species, including Leishmania amazonensis. Treatment of cutaneous leishmaniasis is far from satisfactory due to increases in drug resistance and relapses, and toxicity of compounds to the host. As a consequence for this situation, the development of new leishmanicidal drugs and the search of new targets in the parasite biology are important goals. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the mechanism of death pathway induced by the calpain inhibitor MDL28170 on Leishmania amazonensis promastigote forms. The…

Hyperphosphorylation of tau protein by calpain regulation in retina of Alzheimer's disease transgenic mouse.

Aim to investigate phosphorylated tau expression and its pathogenic mechanism in eye of Alzheimer's disease (AD) transgenic mice. Levels of tau, phosphorylated tau and other related factors (p35/p25, Cyclin-dependent kinase 5 (Cdk5), calpain) were observed by western blot. β-Amyloid (Aβ) plaques and neuron-fibrillary tangles (NFTs) in APP/PS1 double transgenic mice were detected by immuno-histochemistry. We found that hyper-expression of phosphorylated tau was detected in retina, and only a few or no expressed in optic nerve, cornea and lens of transgenic mice. Increased senile plaques (Aβ) an…

Regulation of axon degeneration after injury and in development by the endogenous calpain inhibitor calpastatin.

Axon degeneration is widespread both in neurodegenerative disease and in normal neural development, but the molecular pathways regulating these degenerative processes and the extent to which they are distinct or overlapping remain incompletely understood. We report that calpastatin, an inhibitor of calcium-activated proteases of the calpain family, functions as a key endogenous regulator of axon degeneration. Calpastatin depletion was observed in degenerating axons after physical injury, and maintaining calpastatin inhibited degeneration of transected axons in vitro and in the optic nerve in v…

Mechanism of pyrethroid pesticide-induced apoptosis: role of calpain and the ER stress pathway.

Exposure to the pyrethroid pesticide deltamethrin has been demonstrated to cause apoptosis both in vitro and in vivo. However, the molecular … n exposure activated caspase-12 activity and that pharmacological inhibition and siRNA knockdown of calpain prevented deltamethrin-induced DNA fragmentation, thus indicating a role for the endoplasmic reticulum (ER) stress pathway. This was confirmed by the observation that inhibition of eIF2α abolished deltamethrin-induced DNA fragmentation. Together, th …

[Association of the calpain-10 gene polymorphism with glucose metabolism disorder in pregnant women].

OBJECTIVE: To study three single nucleotide polymorphisms (SNP), SNP-43, -19 and -63 of calpain-10 (CAPN10) gene in pregnant women with glucose metabolism disorders and their relationship with the risk of these disorders. METHODS: Totally, 270 pregnant women including 156 with an abnormal oral glucose tolerance test (study group) and 114 healthy controls were selected among those delivered at the Department of Obstetrics and Gynecology, Peking University First Hospital from Jan. 2005 to Dec. 2006. The SNP of CAPN10 gene at positions 43, 19, and 63 were analyzed by primer-introduced restrictio…

Activation of calpain and caspase pathways in demyelination and neurodegeneration in animal model of multiple sclerosis.

Experimental autoimmune encephalomyelitis (EAE), a widely recognized animal model of multiple sclerosis (MS), is highly useful for studying … iseases harbor a neurodegenerative component. Recent studies also have shown that the activation of calpain and caspase pathways contribute to the apoptotic death of oligodendrocytes and neurons, promoting the pathological events leading to neurological deficits. Apoptosis is involved in the disease-regulating as well as in the disease-promoting processes …

Activation of proteolysis by calpains and structural changes in human paroxysmal and persistent atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is accompanied by electrical, structural and ion-channel protein remodeling. We tested if proteolysis by calpain and proteasome is activated during AF, and studied the relation with the remodeling processes. METHODS: Right atrial appendages were obtained from patients with paroxysmal (n=7) or persistent (n=10) lone AF and compared to controls (n=10) in sinus rhythm undergoing coronary artery bypass grafting (CABG). Proteolysis was measured using Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. Protein expression of calpain I and II was assessed by Western-blo…

Involvement of calpain for apoptosis in dysfunction of the unaffected testis in rats with experimental testicular torsion.

PROBLEM: The dynamics of calpain and involvement of apoptosis in sperm formation disorder of the unaffected testis in rats with experimental testicular torsion were investigated. METHODS OF STUDY: Using 6-week-old Wistar rats, an experimental unilateral testicular torsion model was prepared. The bilateral testes were excised 1, 3, 5, 7, 14, 35, and 70 days after the left testis was twisted, and the unaffected testes were subjected to immunohistological staining, sodium dodecyl sulfate polyacrilamide gel electrophoresis and Western blotting using anti-calpain antibodies. Apoptosis was detected…

Basigin (CD147) and calpain 4 (CapnS1) are partners in the generation of traction force but not in mechanosensing.

Traction force and mechanosensing (the ability to sense the mechanical attributes of the environment) are two key factors that enable a cell to modify its behavior during migration. Previously, it was determined that the calpain small subunit, Calpain 4 (CapnS1), regulates traction force production independent of its proteolytic holoenzyme. A proteolytic enzyme is formed by Calpain 4 binding to either of its catalytic partners, Calpain 1 and 2. To further understand how Calpain 4 regulates traction force, we used two-hybrid analysis to identify more components of the traction pathway. We disco…

Calpain inhibition in a transgenic model of calpastatin overexpression facilitates reversal of myocardial hypertrophy.

AIMS: It was recently demonstrated that the intracellular signalling phosphatase calcineurin is subject to cleavage by the protease calpain, resulting in a truncated calcineurin fragment that is a strong inductor of myocardial hypertrophy. We now address the question of whether inhibition of calpain function in cardiomyocytes, and thereby prevention of calcineurin truncation, attenuates development of myocardial hypertrophy. METHODS AND RESULTS: We generated a transgenic mouse model with conditional cardiac calpastatin overexpression (CAST OE) and compared their cardiac hypertrophic response …

Mitochondria-associated endoplasmic reticulum membrane (MAM)-associated calpains system in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a multisystem disorder characterized primarily by hypertension and proteinuria after 20 weeks of gestation, … tase-polymerase chain reaction (RT-qPCR) was used to validate biomarker expression in PE placentas. Calpain-1, calpain-2, and calpastatin expression levels were evaluated using Immunofluorescence and Western blotting techniques. RESULTS: The results showed early-onset PE (EOPE) had higher abnormal pregnancy history, fetal growth restriction, systolic/dia …

Calpain activity in plasma of patients with essential tremor and Parkinson's disease: a pilot study.

Background: Essential tremor (ET) and Parkinson's disease (PD) are the two most common movement disorders in adults with similar clinical symptoms, which is hinting towards existence of coincident pathogenesis steps.Objectives: The objective of this report is to characterize the relationship between ET and PD severity and the activity of calcium-dependent proteases calpain in plasma.Methods: The study enrolled 12 volunteers for each condition: ET, PD, healthy. We evaluated the stage of PD on the H&Y scale in patients with PD, and the severity of tremor in patients with ET on the FTMS scale. IL…

Calpain Inhibition Is Protective in Machado-Joseph Disease Zebrafish Due to Induction of Autophagy.

The neurodegenerative disease Machado-Joseph disease (MJD), also known as spinocerebellar ataxin-3, affects neurons of the brain and spinal … es a valuable readout for drug treatment studies. Treating the EGFP-ataxin-3-84Q zebrafish with the calpain inhibitor compound calpeptin decreased levels of ataxin-3 cleavage fragments, but also removed all human ataxin-3 protein (confirmed by ELISA) and prevented the early MJD zebrafish motor phenotype. We identified that this clearance of ataxin-3 prote …

[Calpain as a new therapeutic target for treating spasticity after a spinal cord injury].

After a spinal cord injury (SCI), patients develop spasticity, a motor disorder characterized by hyperreflexia and stiffness of muscles. Spasticity results from alterations in motoneurons with an upregulation of their persistent sodium current (I NaP), simultaneously with a disinhibition caused by a reduction of expression of chloride (Cl-) co-transporters KCC2. Until recently the origin of alterations was unknown. After reviewing pathophysiology of spasticity, the manuscript relates our recent work showing a tight relationship between the calpain-dependent proteolysis of voltage-gated sodium …