Animals ; Calpain ; Humans ; Nervous System Diseases ; chemically induced ; Organophosphate Poisoning

Calpains are intracellular nonlysosomal Ca(2+-) regulated cysteine proteases, widely located in the tissues of most mammals. Skeletal muscle tissue mainly expresses m-calpain, µ-caplain, n-calpain, and their endogenous inhibitor calpastatin. They are closely related to the cell apoptosis, cytoskeleton formation, cell cycles, etc. Calpains are also considered to be participating in the protein degradation process. Severe burns are typically followed by hypermetabolic responses that are characterized by hyperdynamic circulatory responses with increased proteolysis and cell apoptosis. Recently, overloading of Ca(2+) in skeletal muscle cells, which activates the calpains is observed after a serious burn. This paper aims to review the current research of the relationship between calpains and post-burn skeletal muscle wasting from the perspectives of structure, function, and physiological activities.
Animals ; Burns ; metabolism ; pathology ; Calpain ; metabolism ; Muscle, Skeletal ; metabolism ; pathology

Calbindin-D28K has been implicated in the regulation of neuronal cell death. Previously, we demonstrated that calbindin-D28K prevents staurosporine (STS)-induced caspase activation and subsequent apoptosis in a neuronal cell line. However, the role of calbindin-D28K in STS-induced activation of calpain and necrotic cell death was not identified. Staurosporine induced the elevation of intracellular calcium after 1 hr of treatment. Overexpression of calbindin-D28K and presence of a calcium chelator, BAPTA, prevented the increase of calcium in STS-treated cells. Cleavage of Bax by calpain was prevented by the overexpressed calbindin-D28K. Permeabilization of the plasma membrane, a factor in necrosis, as well as apoptotic change of the nucleolus induced by STS, was prevented by calbindin-D28K. Thus, our study suggests that calbindin-D28K may exert its protective functions by preventing calpain activation in necrotic cell death, in addition to its effect on the caspase-apoptosis pathway.
Apoptosis ; Calbindin 1* ; Calcium ; Calpain ; Cell Death ; Cell Line ; Cell Membrane ; Membranes* ; Necrosis ; Neurons ; Staurosporine

The calcium-sensitive neutral protease, calpain, is activated in the basilar artery after subarachnoid hemorrhage. Pathological activation of this proteolytic enzyme has been suggested to contribute to cerebral vasospasm after subarachnoid hemorrhage. The present study was undertaken to evaluate the effects of a newly developed calpain inhibitor, CX-287 on vasospasm. A blind, randomized trial was utilized in which CX-287 was injected intravenously into subarachnoid hemorrhage rabbits. Two days after subarachnoid hemorrhage, animals were sacrificed by perfusion-fixation and cross-sectional areas of the basilar arteries were measured using histological techniques. Expressing the cross-sectional area in the untreated SAH animals as a percentage of control value, it was 38.4+/-5.7%. Basilar artery area of the treatment groups with 1.5mg/kg CX-287(b.i.d. or t.i.d) showed no statistical differences from subarachnoid only group(b.i.d.: 34.7%, t.i.d.: 49.0%). However, the treatment group with 3mg/kg CX-287 showed significant reversal of the subarachnoid hemorrhage-induced constriction(b.i.d.: 73.4%, p<0.0003, t.i.d.: 58.7%, p<0.05). These findings support the important role of calcium activated proteolysis by calpain in the pathophysiology of vasospasm after subarachnoid hemorrhage. Furthermore, these results provide the first demonstration that a calpain inhibitor can inhibit cerebral vasospasm.
Animals ; Basilar Artery ; Calcium ; Calpain* ; Histological Techniques ; Injections, Intravenous ; Proteolysis ; Rabbits ; Subarachnoid Hemorrhage* ; Vasospasm, Intracranial

OBJECTIVETo investigate the relationship between the protein expression of calpain-2 and calcineurin (CaN) and atrial fibrillation (AF) in patient with valvular heart disease (VHD).

METHODSA total of 40 patients who underwent valve replacement surgery in our hospital from March 2013 to March 2014, right atrial appendages were excised during operation and patients were divided into sinus rhythm (SR) group (n = 17) and AF group (n = 23). The protein expression of calpain-2 and the α-isoform of CaN catalytic subunit (CnA) in the right atrial appendages were determined by Western blot.

RESULTSThe protein levels of the full-length CnAa (60,000), the 45,000 fragment of CnAa without autoinhibitory domain, and calpain-2 were significantly upregulated in the AF group compared to the SR group (1.25 ± 0.51 vs. 0.76 ± 0.37, 1.08 ± 0.37 vs. 0.76 ± 0.25, and 0.82 ± 0.44 vs. 0.51 ± 0.19, respectively, all P < 0.05).

CONCLUSIONActivated calpain-2-CaN signal pathway might be involved in the pathogenesis of AF.

Atrial Appendage ; Atrial Fibrillation ; Blotting, Western ; Calcineurin ; Calpain ; Heart Valve Diseases ; Humans ; Up-Regulation

OBJECTIVETo investigate the effect of N,N-dimethylformamide (DMF) on calcium homeostasis and calpain I and II gene expression in human hepatocytes (HL-7702).

METHODSHL-7702 cells were exposed to different concentrations of DMF (10, 25, 50, 100, or 200 mmol/L); other HL-7702 cells, which were used as a control group, were exposed to the equal volume of DMEM; the intracellular Ca(2+) concentration was monitored using the calcium fluorescent probe (fluo-3/AM). After 24-h exposure to DMF (10, 25, 50, 100, 150, or 200 mmol/L), the morphology of hepatocytes was observed under an inverted phase contrast microscope, and the cell viability was measured by MTT assay. After 24-h exposure to DMF (10, 25, 50, 100, or 150 mmol/L), the mRNA expression levels of calpain I and II in hepatocytes were measured by real-time quantitative PCR.

RESULTSThere were significant differences in cell viability among different exposure groups (P < 0.01); the 50, 100, 150, and 200 mmol/L DMF exposure groups had a significantly lower cell viability than the control group (P < 0.05). Under the inverted phase contrast microscope, HL-7702 cells gradually lost the original shape, with swelling and shrinking, as the dose of DMF increased, and those treated with 150 mmol/L DMF even became round and floated. The fluorescence density of fluo-3 in hepatocytes increased as the dose of DMF rose, demonstrating a dose-response relationship, and there were significant differences among these exposure groups (P < 0.05). There were significant differences in mRNA expression levels of calpain I and II among these exposure groups (P < 0.01), and the expression increased as the dose of DMF rose; but DMF did not promote the mRNA expression of calpain I at a concentration of 150 mmol/L.

CONCLUSIONDMF can cause damage to hepatocytes, which is related to intracellular calcium increase and calpain mRNA increase.

Calcium ; metabolism ; Calpain ; metabolism ; Cell Line ; Dimethylformamide ; pharmacology ; Hepatocytes ; drug effects ; metabolism ; Humans

OBJECTIVETo investigate the time course of calpain activity changes in rat neurons following fluid percussion injury (FPI) under normothermia (37 degrees celsius;) and mild hypothermia (32-/+0.5) degrees celsius;.

METHODSIn vitro cultured rat neurons were subjected to FPI followed by application of mild hypothermia for intervention at different time points, and the changes in intraneuronal calpain activity following FPI and the interventional effect of mild hypothermia on calpain activity were evaluated by UV-spectrophotometry at different time points.

RESULTSRemarkable changes occurred in calpain activity in the neurons following FPI at 37 degrees celsius;, and mild hypothermia produced obvious interventional effect on calpain activity in close relation to the timing of intervention initiation.

CONCLUSIONIntraneuronal calpain activity changes following FPI are involved in the pathological process of cellular injury, and mild hypothermia might offer protection against traumatic brain injury to some extent by regulating calpain activity. The interventional effect of mild hypothermia is associated with the timing of the intervention initiation.

Animals ; Calpain ; metabolism ; Female ; Hypothermia, Induced ; Neurons ; metabolism ; pathology ; Percussion ; Pregnancy ; Rats ; Rats, Wistar ; Time Factors

Calpain ; genetics ; Diabetes, Gestational ; genetics ; Female ; Genotype ; Haploidy ; Humans ; Polymorphism, Single Nucleotide ; Pregnancy

Animals ; Calpain ; metabolism ; Epithelial Cells ; metabolism ; Kidney ; cytology ; Kidney Tubules ; cytology ; metabolism ; Rats ; Reperfusion Injury ; metabolism

Caspase independent cell death (CICD) is defined as death that ensues when a signal that normally induces apoptosis fails to activate caspases,it can be activated by PARP-1, Calpains, Bax and AIF, possessing distinctive biologic characteristic differed from apoptosis and necrosis. Recent researchs have found that the molecular mechanisms governing CICD of K562 is opposite from that of the traditional medicine killing leukemia cells, which may have the potential pharmaceutical point for new drugs. This article reviews the newly acquaintance of molecular mechanisms for CICD and recent studies concerning the induction death of K562 cells via CICD, so as to provide some reference for the research of new drug point.
Apoptosis ; Calpain ; Caspases ; Humans ; K562 Cells ; Necrosis ; Poly(ADP-ribose) Polymerases ; bcl-2-Associated X Protein