Search results for "Sarcoplasmic Reticulum"
showing 10 items of 17 documents
Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations
2016
This work was supported by Spanish Ministry of Economy and Competitiveness (MINECO) Grants SAF2010-16044 and SAF2013-46663-R (to V.A.), SAF2011-30312 and SAF2014-58286-C2-1-R (to L.H.-M.), SAF2011-30088 (to E.D.), and SAF2014-52413-R (to C.L.-O.) and Fondo de Investigación Sanitaria del Instituto de Salud Carlos III Grants RD12/0042/0028 (to V.A.), RD12/0042/0011 (to J.T.), and RD12/0042/0002 (to L.H.-M.), with cofunding from the Fondo Europeo de Desarrollo Regional and the Progeria Research Foundation. J.A.G. is the recipient of a U-Mobility Grant from the Marie Curie cofunding of Regional, National and International Programme (Grant 246550). The Instituto Universitario de Oncología is sup…
SERCA and P-glycoprotein inhibition and ATP depletion are necessary for celastrol-induced autophagic cell death and collateral sensitivity in multidr…
2019
Multidrug resistance (MDR) represents an obstacle in anti-cancer therapy. MDR is caused by multiple mechanisms, involving ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp), which reduces intracellular drug levels to sub-therapeutic concentrations. Therefore, sensitizing agents retaining effectiveness against apoptosis- or drug-resistant cancers are desired for the treatment of MDR cancers. The sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump is an emerging target to overcome MDR, because of its continuous expression and because the calcium transport function is crucial to the survival of tumor cells. Previous studies showed that SERCA inhibitors exhibit anti-c…
Oxidative modification impairs SERCA activity in Drosophila and human cell models of Parkinson's disease
2021
DJ-1 is a causative gene for familial Parkinson's disease (PD) with different functions, standing out its role against oxidative stress (OS). Accordingly, PD model flies harboring a mutation in the DJ-1β gene (the Drosophila ortholog of human DJ-1) show high levels of OS markers like protein carbonylation, a common post-translational modification that may alter protein function. To increase our understanding of PD pathogenesis as well as to discover potential therapeutic targets for pharmacological intervention, we performed a redox proteomic assay in DJ-1β mutant flies. Among the proteins that showed increased carbonylation levels in PD model flies, we found SERCA, an endoplasmic reticulum…
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…
Ultrastructural pathology in emetine-induced myopathy
1988
Progressive myopathy developed in two women who consumed ipecac syrup containing emetine hydrochloride to induce vomiting as part of their anorexia nervosa. Muscle biopsy specimens were characterized by severe disruption of the sarcomeres. The ultrastructural spectrum extended from "Z-band streaming" to the formation of cytoplasmic bodies and also comprised abnormalities of the sarcotubular system, thus suggesting that muscle weakness may be related to both sarcomeric and sarcotubular lesions in this self-inflicted myopathy. It is tempting to suggest that muscle weakness may be correlated with or based on the pathology in sarcomeres and the sarcotubular system. As the myopathy is clinically…
Identification of fish species by reversed-phase high-performance liquid chromatography with photodiode-array detection
1998
A method for the separation of sarcoplasmic fish proteins by RP-HPLC is described. The procedure revealed significant differences useful for reliable identification of fish species. Sixteen of the most common Finnish freshwater fish species were differentiated by species-specific HPLC chromatograms obtained using photodiode-array detection (PAD) at 200-350 nm. The analytical column was a Hi-Pore RP-304 reversed-phase column. The separation was performed by a linear gradient of acetonitrile and water with a small amount of trifluoracetic acid (TFA). Star-symbol plots were constructed from the chromatograms to visualize the data. Clearly different HPLC protein profiles for most fish species w…
Reversible stress-induced lipid body formation in fast twitch rat myofibers
2012
We analyzed the existence of lipid bodies (LBs) in the fast twitch rat flexor digitorum brevis (FDB) myofibers and found that these structures were scarce. However, isolation procedure of the myofibers, heath shock, viral infection or the glycosylation inhibitor tunicamycin induced formation of the LBs, which were stationary structures flanking Z lines. We next infected FDB myofibers with recombinant Semliki Forest virus expressing caveolin 3-yellow fluorescent protein (cav3-YFP) since this chimeric protein was targeted to the LBs facilitating their further analysis. Photobleaching experiments showed that the LBs recovered cav 3-YFP extremely slowly, indicating that they were not continuous…
Paradoxical effect of increased diastolic Ca(2+) release and decreased sinoatrial node activity in a mouse model of catecholaminergic polymorphic ven…
2012
Background— Catecholaminergic polymorphic ventricular tachycardia is characterized by stress-triggered syncope and sudden death. Patients with catecholaminergic polymorphic ventricular tachycardia manifest sinoatrial node (SAN) dysfunction, the mechanisms of which remain unexplored. Methods and Results— We investigated SAN [Ca 2+ ] i handling in mice carrying the catecholaminergic polymorphic ventricular tachycardia–linked mutation of ryanodine receptor (RyR2 R4496C ) and their wild-type (WT) littermates. In vivo telemetric recordings showed impaired SAN automaticity in RyR2 R4496C mice after isoproterenol injection, analogous to what was observed in catecholaminergic polymorphic ventricul…
Expression Profile of Stress Proteins, Intermediate Filaments, and Adhesion Molecules in Experimentally Denervated and Reinnervated Rat Facial Muscle
1997
The immunohistochemical profiles of ubiquitin, heat shock protein 70, alpha-B-crystallin, desmin, vimentin, neural cell adhesion molecule (N-CAM), and tenascin in rat facial muscle were studied after permanent denervation by transection of the facial plexus on one side and compared with findings after immediate reinnervation by hypoglossal-facial nerve anastomosis subsequent to transection on the contralateral side. Levator labii muscle samples were collected sequentially at 2, 6, 7, 10, 20, and 24 weeks after surgery. Normal levator labii muscle fibers showed physiological expression of desmin and alpha-B-crystallin. Denervated rat facial muscle displayed distinct up-regulation of ubiquiti…
Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation
2021
Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca 2+ release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2 R420Q . Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in …