PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 31658977-7 2019 Nrf2 activation in SOD1 mutant astrocytes with dimethyl fumarate restores calcium homeostasis and ameliorates motor neuron death. Calcium 74-81 superoxide dismutase 1 Homo sapiens 19-23 31658977-8 2019 These results highlight a regulatory mechanism of intracellular calcium homeostasis by ER redox signaling and suggest that this mechanism could be a therapeutic target in SOD1 mutant astrocytes. Calcium 64-71 superoxide dismutase 1 Homo sapiens 171-175 27083773-11 2016 We observed SOD1(G93A) astrocytes exhibited enhanced gap junction coupling, increased hemichannel-mediated activity, and elevated intracellular calcium levels. Calcium 144-151 superoxide dismutase 1 Homo sapiens 12-16 29870639-0 2017 [Calcium ion is a common denominator in the pathophysiological processes of amyotrophic lateral sclerosis]. Calcium 1-8 superoxide dismutase 1 Homo sapiens 76-105 29870639-7 2017 This review provides an overview of the role of calcium in connecting and amplifying the major mechanisms which lead to degeneration of the motor neurons in ALS. Calcium 48-55 superoxide dismutase 1 Homo sapiens 157-160 28482850-2 2017 Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. Calcium 195-202 superoxide dismutase 1 Homo sapiens 141-145 26106294-2 2015 We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1(G93A) (ACM-hSOD1(G93A)) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Calcium 250-257 superoxide dismutase 1 Homo sapiens 166-170 26388731-5 2015 The latter issue was recently investigated in relationship with altered calcium homeostasis and autophagy, which affect mitochondria in ALS. Calcium 72-79 superoxide dismutase 1 Homo sapiens 136-139 26388731-11 2015 Thus, recent findings related to altered calcium storage and impaired autophagy flux in ALS may help to understand the occurrence of mitochondrial alterations as a hallmark in ALS patients. Calcium 41-48 superoxide dismutase 1 Homo sapiens 176-179 26106294-2 2015 We showed earlier that exposing primary rat spinal cord cultures to conditioned media derived from primary mouse astrocyte conditioned media (ACM) that express human SOD1(G93A) (ACM-hSOD1(G93A)) quickly enhances Nav channel-mediated excitability and calcium influx, generates intracellular reactive oxygen species (ROS), and leads to death of motoneurons within days. Calcium 250-257 superoxide dismutase 1 Homo sapiens 182-187 26106294-9 2015 Together, our data point to a sequence of events in which a toxic factor(s) released by ALS-expressing astrocytes rapidly induces hyper-excitability, which in turn increases calcium influx and affects mitochondrial structure and physiology. Calcium 174-181 superoxide dismutase 1 Homo sapiens 88-91 24716897-0 2014 The voltage-gated calcium channel blocker lomerizine is neuroprotective in motor neurons expressing mutant SOD1, but not TDP-43. Calcium 18-25 superoxide dismutase 1 Homo sapiens 107-111 25463043-0 2015 Calcium binding to gatekeeper residues flanking aggregation-prone segments underlies non-fibrillar amyloid traits in superoxide dismutase 1 (SOD1). Calcium 0-7 superoxide dismutase 1 Homo sapiens 117-139 25463043-0 2015 Calcium binding to gatekeeper residues flanking aggregation-prone segments underlies non-fibrillar amyloid traits in superoxide dismutase 1 (SOD1). Calcium 0-7 superoxide dismutase 1 Homo sapiens 141-145 25463043-2 2015 Calcium accumulates in the spinal and brain stem motor neurons of ALS patients triggering multiple pathophysiological processes which have been recently shown to include direct effects on the aggregation cascade of superoxide dismutase 1 (SOD1). Calcium 0-7 superoxide dismutase 1 Homo sapiens 215-237 25463043-2 2015 Calcium accumulates in the spinal and brain stem motor neurons of ALS patients triggering multiple pathophysiological processes which have been recently shown to include direct effects on the aggregation cascade of superoxide dismutase 1 (SOD1). Calcium 0-7 superoxide dismutase 1 Homo sapiens 239-243 26056593-3 2014 The existing evidence suggests that the mutant superoxide dismutase1 (mtSOD1)-mediated toxicity in ALS acts through mitochondria, and that alteration in cytosolic and mitochondria-ER microdomain calcium accumulation are critical to the neurodegenerative process. Calcium 195-202 superoxide dismutase 1 Homo sapiens 47-68 24148000-2 2014 Pathological changes in ALS are closely associated with pronounced and progressive changes in mitochondrial morphology, bioenergetics and calcium homeostasis. Calcium 138-145 superoxide dismutase 1 Homo sapiens 24-27 23578819-0 2013 Overexpression of human mutated G93A SOD1 changes dynamics of the ER mitochondria calcium cycle specifically in mouse embryonic motor neurons. Calcium 82-89 superoxide dismutase 1 Homo sapiens 37-41 24501372-0 2014 Abnormal intracellular calcium signaling and SNARE-dependent exocytosis contributes to SOD1G93A astrocyte-mediated toxicity in amyotrophic lateral sclerosis. Calcium 23-30 superoxide dismutase 1 Homo sapiens 87-91 24501372-4 2014 We found that purinergic stimulation induces excess calcium release from the ER stores in SOD1G93A astrocytes, which results from the abnormal ER calcium accumulation and is independent of clearance mechanisms. Calcium 52-59 superoxide dismutase 1 Homo sapiens 90-94 24501372-4 2014 We found that purinergic stimulation induces excess calcium release from the ER stores in SOD1G93A astrocytes, which results from the abnormal ER calcium accumulation and is independent of clearance mechanisms. Calcium 146-153 superoxide dismutase 1 Homo sapiens 90-94 24501372-6 2014 We found that oxidant-induced increased S-glutathionylation and calcium-independent puncta formation of the ER calcium sensor STIM1 underlies the abnormal SOCE response in SOD1G93A astrocytes. Calcium 64-71 superoxide dismutase 1 Homo sapiens 172-176 24501372-6 2014 We found that oxidant-induced increased S-glutathionylation and calcium-independent puncta formation of the ER calcium sensor STIM1 underlies the abnormal SOCE response in SOD1G93A astrocytes. Calcium 111-118 superoxide dismutase 1 Homo sapiens 172-176 24501372-7 2014 Enhanced SOCE contributes to ER calcium overload in SOD1G93A astrocytes and excess calcium release from the ER during ATP stimulation. Calcium 32-39 superoxide dismutase 1 Homo sapiens 52-56 24032595-4 2014 Purified TG2 directly oligomerized recombinant mutant SOD1 and the apo-form of the wild-type SOD1 proteins in a calcium-dependent manner, indicating that misfolded SOD1 is a substrate of TG2. Calcium 112-119 superoxide dismutase 1 Homo sapiens 54-58 24032595-4 2014 Purified TG2 directly oligomerized recombinant mutant SOD1 and the apo-form of the wild-type SOD1 proteins in a calcium-dependent manner, indicating that misfolded SOD1 is a substrate of TG2. Calcium 112-119 superoxide dismutase 1 Homo sapiens 93-97 24032595-4 2014 Purified TG2 directly oligomerized recombinant mutant SOD1 and the apo-form of the wild-type SOD1 proteins in a calcium-dependent manner, indicating that misfolded SOD1 is a substrate of TG2. Calcium 112-119 superoxide dismutase 1 Homo sapiens 93-97 23578819-3 2013 We analysed ER mitochondria calcium cycle (ERMCC) dynamics with subsecond resolution in G93A hSOD1 overexpressing motor neurons as a model of ALS using fluorescent calcium imaging. Calcium 28-35 superoxide dismutase 1 Homo sapiens 93-98 23578819-4 2013 When comparing vulnerable motor neurons and non-motor neurons from G93A hSOD1 mice and their non-transgenic littermates, we found a decelerated cytosolic calcium clearance in the presence of G93A hSOD1. Calcium 154-161 superoxide dismutase 1 Homo sapiens 72-77 23578819-5 2013 While both non-transgenic as well as G93A hSOD1 motor neurons displayed large mitochondrial calcium uptake by the mitochondrial uniporter (mUP), the mitochondrial calcium extrusion system was altered in the presence of G93A hSOD1. Calcium 92-99 superoxide dismutase 1 Homo sapiens 42-47 23578819-6 2013 In addition, ER calcium uptake by the sarco-/endoplasmic reticulum ATPase (SERCA) was increased in G93A hSOD1 motor neurons. Calcium 16-23 superoxide dismutase 1 Homo sapiens 104-109 23578819-8 2013 Thus, our study shows for the first time that the functional consequence of G93A hSOD1 overexpression in intact motor neurons is indeed a disturbance of the ER mitochondria calcium cycle, and identified two promising targets for therapeutic intervention in the pathology of ALS. Calcium 173-180 superoxide dismutase 1 Homo sapiens 81-86 23861388-0 2013 Calcium ions promote superoxide dismutase 1 (SOD1) aggregation into non-fibrillar amyloid: a link to toxic effects of calcium overload in amyotrophic lateral sclerosis (ALS)? Calcium 0-7 superoxide dismutase 1 Homo sapiens 21-43 23861388-0 2013 Calcium ions promote superoxide dismutase 1 (SOD1) aggregation into non-fibrillar amyloid: a link to toxic effects of calcium overload in amyotrophic lateral sclerosis (ALS)? Calcium 0-7 superoxide dismutase 1 Homo sapiens 45-49 23147108-2 2013 Previously, we showed that antioxidant enzyme Cu-Zn superoxide dismutase (SOD1) is secreted by many cellular lines and specifically interacts with cell surface membrane of human neuroblastoma SK-N-BE cells thus activating phospholipase C (PLC) transduction pathway and increasing intracellular calcium concentration ([Ca(2+)](i)). Calcium 294-301 superoxide dismutase 1 Homo sapiens 46-72 23486205-4 2013 Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1(G93A)) increases persistent sodium inward currents (PC(Na)), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. Calcium 253-260 superoxide dismutase 1 Homo sapiens 139-143 23486205-4 2013 Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1(G93A)) increases persistent sodium inward currents (PC(Na)), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. Calcium 253-260 superoxide dismutase 1 Homo sapiens 149-154 23147108-2 2013 Previously, we showed that antioxidant enzyme Cu-Zn superoxide dismutase (SOD1) is secreted by many cellular lines and specifically interacts with cell surface membrane of human neuroblastoma SK-N-BE cells thus activating phospholipase C (PLC) transduction pathway and increasing intracellular calcium concentration ([Ca(2+)](i)). Calcium 294-301 superoxide dismutase 1 Homo sapiens 74-78 22015651-3 2012 Previous data showed that SOD1 is secreted by many cellular lines, including neuroblastoma SK-N-BE cells through microvesicles by an ATP-dependent mechanism; moreover, it has been shown that SOD1 interacts with human neuroblastoma cell membranes increasing intracellular calcium levels via a phospholipase C-protein kinase C pathway activation. Calcium 271-278 superoxide dismutase 1 Homo sapiens 26-30 22015651-3 2012 Previous data showed that SOD1 is secreted by many cellular lines, including neuroblastoma SK-N-BE cells through microvesicles by an ATP-dependent mechanism; moreover, it has been shown that SOD1 interacts with human neuroblastoma cell membranes increasing intracellular calcium levels via a phospholipase C-protein kinase C pathway activation. Calcium 271-278 superoxide dismutase 1 Homo sapiens 191-195 19545440-3 2009 The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. Calcium 217-224 superoxide dismutase 1 Homo sapiens 84-88 21943126-3 2011 Here, we present the first evidence of the effects of overexpression of mutant (TG G93A) and wild type (TG WT) human SOD1 transgenes on a set of functional properties of microglia relevant to ALS progression, including expression of integrin beta-1, spreading and migration, phagocytosis of apoptotic neuronal cell debris, and intracellular calcium changes in response to an inflammatory stimulus. Calcium 341-348 superoxide dismutase 1 Homo sapiens 117-121 18808448-7 2008 While intra-mitochondrial calcium levels [Ca(2+)](m) were elevated in SOD1(G93A) motoneurons, changes in mitochondrial function did not correlate with [Ca(2+)](m). Calcium 26-33 superoxide dismutase 1 Homo sapiens 70-74 18059133-0 2007 Calcium-influx increases SOD1 aggregates via nitric oxide in cultured motor neurons. Calcium 0-7 superoxide dismutase 1 Homo sapiens 25-29 18059133-7 2007 Our data demonstrate that calcium-influx increases SOD1 aggregation by upregulating NO in cultured motor neuronal cells. Calcium 26-33 superoxide dismutase 1 Homo sapiens 51-55 16199912-4 2005 Regarding the mechanism for this kind of action by nifedipine (a calcium antagonist), it seems likely that the drug stimulates SOD expression in endothelial cells through enhanced VEGF expression by vascular smooth muscle cells, and thus reduces oxidative stress, leading to increased NO production. Calcium 65-72 superoxide dismutase 1 Homo sapiens 127-130 16546142-1 2006 Immunohistochemical study was performed to examine if calcium-binding proteins are involved in the degeneration of motor neurons in the brain stems and the spinal cords of transgenic mice carrying a G93A mutant human SOD1 gene. Calcium 54-61 superoxide dismutase 1 Homo sapiens 217-221 12561164-6 2002 The photophosphorylation activity increased when the concentration of calcium ion in reaction medium ranged from 0 to 6 mmol.L-1, and peaked at the 4.5 mmol.L-1, while superoxidase dismutase (SOD) activity rose from 0 to 6 mmol.L-1 and peaked at 6 mmol.L-1. Calcium 70-77 superoxide dismutase 1 Homo sapiens 168-190 15474511-0 2004 Cu,Zn superoxide dismutase increases intracellular calcium levels via a phospholipase C-protein kinase C pathway in SK-N-BE neuroblastoma cells. Calcium 51-58 superoxide dismutase 1 Homo sapiens 0-26 15474511-4 2004 By analyzing the surface binding of biotinylated SOD1 on SK-N-BE cells and by measuring intracellular calcium concentrations and PKC activity, we demonstrated that SOD1 specifically interacts in a dose-dependent manner with the cell surface membrane of SK-N-BE. Calcium 102-109 superoxide dismutase 1 Homo sapiens 164-168 15474511-7 2004 On the whole, these data indicate that SOD1 carries out a neuromodulatory role affecting calcium-dependent cellular functions. Calcium 89-96 superoxide dismutase 1 Homo sapiens 39-43 12561164-6 2002 The photophosphorylation activity increased when the concentration of calcium ion in reaction medium ranged from 0 to 6 mmol.L-1, and peaked at the 4.5 mmol.L-1, while superoxidase dismutase (SOD) activity rose from 0 to 6 mmol.L-1 and peaked at 6 mmol.L-1. Calcium 70-77 superoxide dismutase 1 Homo sapiens 192-195 10574366-1 1999 Altered calcium homeostasis has been demonstrated in human spinal cord motor axon terminals of ALS patients, in spinal motor neurons of mutant SOD transgenic mice and following injection of ALS immunoglobulins. Calcium 8-15 superoxide dismutase 1 Homo sapiens 143-146 12151755-0 2002 Alteration in intracellular calcium homeostasis reduces motor neuronal viability expressing mutated Cu/Zn superoxide dismutase through a nitric oxide/guanylyl cyclase cGMP cascade. Calcium 28-35 superoxide dismutase 1 Homo sapiens 100-126 12151755-2 2002 The accumulation of intracellular calcium is one of the primary mechanisms of motor neuronal degeneration associated with mutations in SOD-1. Calcium 34-41 superoxide dismutase 1 Homo sapiens 135-140 12151755-10 2002 Our data suggests that motoneuron degeneration with the SOD-1 mutation may be mediated by calcium dysregulation, particularly by the exogenous calcium influx. Calcium 90-97 superoxide dismutase 1 Homo sapiens 56-61 12151755-10 2002 Our data suggests that motoneuron degeneration with the SOD-1 mutation may be mediated by calcium dysregulation, particularly by the exogenous calcium influx. Calcium 143-150 superoxide dismutase 1 Homo sapiens 56-61 11466956-0 2000 Altered calcium homeostasis in ALS as a target for therapy. Calcium 8-15 superoxide dismutase 1 Homo sapiens 31-34 7708768-4 1995 In mammalian neural cells, the overexpression of wild-type SOD1 inhibits apoptosis induced by serum and growth factor withdrawal or calcium ionophore. Calcium 132-139 superoxide dismutase 1 Homo sapiens 59-63 10086395-2 1999 Mice with the G93A human SOD1 mutation have altered electron transport enzymes, and expression of the mutant enzyme in vitro results in a loss of mitochondrial membrane potential and elevated cytosolic calcium concentration. Calcium 202-209 superoxide dismutase 1 Homo sapiens 25-29 9822728-0 1998 Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms. Calcium 105-112 superoxide dismutase 1 Homo sapiens 45-71 9822728-4 1998 Both a general antagonist of AMPA/kainate receptors (CNQX) and a specific antagonist of calcium-permeable AMPA receptors (joro spider toxin) reduced formation of SOD-1 proteinaceous aggregates and prevented death of motor neurons expressing SOD-1 mutants. Calcium 88-95 superoxide dismutase 1 Homo sapiens 162-167 9822728-4 1998 Both a general antagonist of AMPA/kainate receptors (CNQX) and a specific antagonist of calcium-permeable AMPA receptors (joro spider toxin) reduced formation of SOD-1 proteinaceous aggregates and prevented death of motor neurons expressing SOD-1 mutants. Calcium 88-95 superoxide dismutase 1 Homo sapiens 241-246 9804382-7 1998 On the contrary, overexpression of human NF-H proteins was found to confer an effective protection against mutant SOD1 toxicity in transgenic mice, a phenomenon that may be due to the ability of NF proteins to chelate calcium. Calcium 218-225 superoxide dismutase 1 Homo sapiens 114-118 34685754-5 2021 Moreover, we found that both SOD1 mutant MNs showed ALS-specific neurite degenerations and neurotransmitter-induced calcium hyperresponsiveness. Calcium 116-123 superoxide dismutase 1 Homo sapiens 29-33 34669638-6 2021 We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. Calcium 64-71 superoxide dismutase 1 Homo sapiens 135-139 34669638-9 2021 Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease. Calcium 130-137 superoxide dismutase 1 Homo sapiens 34-38