GO:0090534 GO calcium ion-transporting ATPase complex CHEBI:39124 CHEBI calcium ion GO:0005746 GO mitochondrial respiratory chain CHEBI:15422 CHEBI ATP CHEBI:26523 CHEBI reactive oxygen species CHEBI:16480 CHEBI nitric oxide GO:0005388 GO calcium-transporting ATPase activity GO:0006754 GO ATP biosynthetic process GO:1903409 GO reactive oxygen species biosynthetic process GO:0060291 GO long-term synaptic potentiation MP:0003674 MP oxidative stress 2 WIKI decreased 1 WIKI increased 9 WIKI disrupted Lead(II) 2016-11-29T18:42:17 2016-11-29T18:42:17 Inhibition, Ca++ ATPase Molecular <p>Pb(II) has been shown to decrease Ca++ ATPase activity, leading to an increase in intracellular calcium. It is not known exactly how this works; however, it may be through Pb++ competition with Ca++ <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup> </p> CL:0000255 CL eukaryotic cell <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><a href="#cite_ref-1">↑</a></span> <span class="reference-text">He, T, et al. 2009. Chronic lead exposure alters presynaptic calcium regulation and synaptic facilitation in Drosophila larvae. NeuroToxicology 30(5): 777-84.</span> </li> </ol> AOPWiki 2016-11-29T18:41:22 2017-09-16T10:14:40 Increase, Ca++ (intracellular) Cellular <p>Decreased Ca++ ATPase activity leads to an increase in intracellular calcium <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup>. </p> CL:0000255 CL eukaryotic cell <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><a href="#cite_ref-1">↑</a></span> <span class="reference-text">He, T., et al. 2009. Chronic lead exposure alters presynaptic calcium regulation and synaptic facilitation in Drosophila larvae. NeuroToxicology 30(5): 777-84.</span> </li> </ol> AOPWiki 2016-11-29T18:41:22 2017-09-16T10:14:40 Disruption, Mitochondrial electron transport chain Cellular CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:23 2017-09-16T10:14:40 Decrease, Mitochondrial ATP production Cellular CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:22 2017-09-16T10:14:40 Increase, ROS production Molecular CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:23 2021-04-11T18:03:23 Decreased, Nitric Oxide Cellular CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:23 2017-09-16T10:14:40 Decreased, Long-term potentiation (LTP) Organ UBERON:0001016 UBERON nervous system AOPWiki 2016-11-29T18:41:23 2017-09-16T10:14:41 Increased, Oxidative damage Individual AOPWiki 2016-11-29T18:41:24 2016-12-03T16:33:26 <p>The purpose of the Ca++ ATPase is to pump Ca++ out of the cell <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup>,<sup id="cite_ref-2" class="reference"><a href="#cite_note-2">[2]</a></sup>. When the ATPase is inhibited, this will lead to an overall increase (relative) of intracellular calcium. </p> #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b430265a840> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:54 <ul> <li> Mitochondrial electron transport chain disruption follows intracellular Ca++ dysregulation <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup> </li> </ul> #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42eb15d160> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:54 <ul> <li> The mitochondrial electron transport chain facilitates the efficient production of ATP <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup> </li> </ul> #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ea246190> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:55 <ul> <li> Mitochondria tend to leak oxygenated radicals <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup> </li> </ul> #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42ebcd0a38> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:55 <ul> <li> Nitric oxide (NO) is important for Long-term potentiation (LTP). NO synthesase inhibitor administration prevents LTP <sup id="cite_ref-1" class="reference"><a href="#cite_note-1">[1]</a></sup>. </li> </ul> #<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb89dc9d8d0> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:55 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb89f6f0ca0> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:55 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a039c1c0> AOPWiki 2016-11-29T18:41:33 2016-12-03T16:37:56 Calcium-mediated neuronal ROS production and energy imbalance Brendan Ferreri-Hanberry Open for adoption 1.0 <p>Chemicals may lead to neurotoxicity through the inhibition of calcium ATPase activity, leading to increased intracellular calcium, increased ROS, and energy imbalance. This may lead to impaired nuerotransmission and oxidative neuronal damage.</p> adjacent Not Specified High adjacent Not Specified Moderate adjacent Not Specified Moderate adjacent Not Specified Moderate adjacent Not Specified Moderate adjacent Not Specified Low adjacent Not Specified High <p><em>Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps. </em></p> AOPWiki 2016-11-29T18:41:16 2023-09-25T16:26:45