Search results for "Calpain"
showing 10 items of 29 documents
PPAR gamma agonist leriglitazone improves frataxin-loss impairments in cellular and animal models of Friedreich Ataxia
2020
Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by degeneration of the large sensory neurons and spinocerebellar tracts, cardiomyopathy, and increased incidence in diabetes. The underlying pathophysiological mechanism of FRDA, driven by a significantly decreased expression of frataxin (FXN), involves increased oxidative stress, reduced activity of enzymes containing iron‑sulfur clus-ters (ISC), defective energy production, calcium dyshomeostasis, and impaired mitochondrial biogenesis, leading to mitochondrial dysfunction. The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcriptional factor playing a key role in mito…
Cardiac Glycoside Glucoevatromonoside Induces Cancer Type-Specific Cell Death.
2018
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+/K+-ATPase α subunit, assessed by computational docking. GEV-induced cell death was caspase-independent, as investigated by a multiparametric approach, and culminates in severe morphological alterations in A549 cells, monitored by transmission el…
Isoform-specific function of calpains in cell adhesion disruption: studies in postlactational mammary gland and breast cancer.
2016
Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca2+-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, β-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able …
Host Cell Calpains Can Cleave Structural Proteins from the Enterovirus Polyprotein
2019
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 polyprotein. Using purified calpains 1 and 2 in an in vitro assay, we show that addition of calpains leads to an increase in the release of VP1 and VP3 capsid proteins from P1 of enterovirus B species, detected by western blotting. This was prevented with a calpain inhibitor and was dependent on optimal calcium concentration, especially for calpa…
Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in…
2019
Background and purpose Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. Experimental approach We used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca2+ -mediated autophagy were analysed by histological, immunohis…
Effects of fatiguing jumping exercise on mRNA expression of titin-complex proteins and calpains.
2009
Eccentric exercise induced by electrostimulation increases mRNA expression of titin-complex proteins in rodent skeletal muscle. In this study, mRNA expression of titin, muscle LIM protein (MLP), cardiac ankyrin repeat protein (CARP), ankyrin repeat domain protein 2 (Ankrd2), diabetes-related ankyrin repeat protein (DARP), and calcium-activated proteinases, calpains, were investigated in human skeletal muscle after fatiguing jumping exercise. Fatiguing jumping exercise did not change mRNA expression of titin, DARP, calpain 1, or calpain 3. MLP, Ankrd2 and calpain 2 mRNA levels were increased 2 days postexercise. CARP mRNA level was already elevated 30 min and remained elevated 2 days postexe…
Acute change of titin at mid-sarcomere remains despite 8 wk of plyometric training
2014
Purpose: The purpose of this study was to investigate skeletal muscle changes induced by an acute bout of plyometric exercise (PlyEx) both before and after PlyEx training, to understand if titin is affected differently after PlyEx training. Methods: Healthy untrained individuals (N=11) completed the 1stPlyEx (10x10 squat-jumps, 1min rest). Thereafter, 6 subjects completed 8 weeks of PlyEx, while 5 controls abstained from any jumping activity. Seven days after the last training session all subjects completed the 2ndPlyEx. Blood samples were collected before, 6 hours and 1, 2, 3 and 4 days after each acute bout of PlyEx, and muscle biopsies 4 days before and 3 days after each acute bout of Pl…
Impaired calcium homeostasis in aged hippocampal neurons
2009
Abstract Development of neurodegenerative diseases such as Alzheimer's and Parkinson's disease is strongly age-associated. The impairment of calcium homeostasis is considered to be a key pathological event leading to neuronal dysfunction and cell death. However, the exact impact of aging on calcium homeostasis in neurons remains largely unknown. In the present work we have investigated intracellular calcium levels in cultured primary hippocampal neurons from young (2 months) and aged (24 months) rat brains. Upon stimulation with glutamate or hydrogen peroxide aged neurons in comparison to young neurons demonstrated an increased vulnerability to these disease-related toxins. Measurement of c…
Bortezomib induces in HepG2 cells IkappaBalpha degradation mediated by caspase-8.
2006
The present paper demonstrates that the proteasome inhibitor bortezomib, which behaves as an apoptotic agent in hepatoma HepG2 cells, caused in these cells a decrease in IkappaBalpha level and a consequent increase in NF- kappaB activity. The effect already appeared at 4 h of treatment and preceded the onset of apoptosis which was observed at 24 h. Our results demonstrate that bortezomib-induced IkappaBalpha degradation occurred in conjunction with the activation of caspase-8; moreover, the decrease in IkappaBalpha level was prevented in a dose-dependent manner by the addition of z-IETD, a specific inhibitor of caspase-8. Bortezomib caused the same effects in non-tumor Chang liver cells, wh…
Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway
2012
A novel virus- and integrin clustering–specific pathway diverts integrin from its normal endo/exocytic traffic to a nonrecycling degradative endosomal route. Clustering of α2β1 integrin causes redistribution of the integrin to perinuclear endosomes, leading to enhanced integrin turnover promoted by calpains.