{"id":2493,"date":"2014-10-02T22:30:00","date_gmt":"2014-10-02T22:30:00","guid":{"rendered":"https:\/\/scian.cl\/scientific-image-analysis\/?p=2493"},"modified":"2023-06-17T03:17:35","modified_gmt":"2023-06-17T03:17:35","slug":"ryanodine-receptor-mediated-ca2-release-underlies-iron-induced-mitochondrial-fission-and-stimulates-mitochondrial-ca2-uptake-in-primary-hippocampal-neurons","status":"publish","type":"post","link":"https:\/\/scian.cl\/scientific-image-analysis\/ryanodine-receptor-mediated-ca2-release-underlies-iron-induced-mitochondrial-fission-and-stimulates-mitochondrial-ca2-uptake-in-primary-hippocampal-neurons\/","title":{"rendered":"Ryanodine receptor-mediated Ca2+ release underlies iron-induced mitochondrial fission and stimulates mitochondrial Ca2+ uptake in primary hippocampal neurons"},"content":{"rendered":"\n<p>San Mart\u00edn CD, Paula-Lima AC, Garc\u00eda A, H\u00e4rtel S, N\u00fa\u00f1ez MT and C Hidalgo<br>Frontiers in Molecular Neuroscience, 11, 7-13. doi: 10.3389\/fnmol.2014.00013<\/p>\n\n\n<style>.wp-block-kadence-spacer.kt-block-spacer-_b05527-7b .kt-block-spacer{height:60px;}.wp-block-kadence-spacer.kt-block-spacer-_b05527-7b .kt-divider{border-top-width:1px;height:1px;border-top-color:#eee;width:80%;border-top-style:solid;}<\/style>\n<div class=\"wp-block-kadence-spacer aligncenter kt-block-spacer-_b05527-7b\"><div class=\"kt-block-spacer kt-block-spacer-halign-left\"><hr class=\"kt-divider\"\/><\/div><\/div>\n\n\n\n<p><strong>ABSTRACT<\/strong><br>Mounting evidence indicates that iron accumulation impairs brain function. We have reported previously that addition of sub-lethal concentrations of iron to primary hippocampal neurons produces Ca(2) (+) signals and promotes cytoplasmic generation of reactive oxygen species. These Ca(2) (+) signals, which emerge within seconds after iron addition, arise mostly from Ca(2) (+) release through the redox-sensitive ryanodine receptor (RyR) channels present in the endoplasmic reticulum. We have reported also that addition of synaptotoxic amyloid-\u03b2 oligomers to primary hippocampal neurons stimulates RyR-mediated Ca(2) (+) release, generating long-lasting Ca(2) (+) signals that activate Ca(2) (+)-sensitive cellular effectors and promote the disruption of the mitochondrial network. Here, we describe that 24 h incubation of primary hippocampal neurons with iron enhanced agonist-induced RyR-mediated Ca(2) (+) release and promoted mitochondrial network fragmentation in 43% of neurons, a response significantly prevented by RyR inhibition and by the antioxidant agent N-acetyl-L-cysteine. Stimulation of RyR-mediated Ca(2) (+) release by a RyR agonist promoted mitochondrial Ca(2) (+) uptake in control neurons and in iron-treated neurons that displayed non-fragmented mitochondria, but not in neurons with fragmented mitochondria. Yet, the global cytoplasmic Ca(2) (+) increase induced by the Ca(2) (+) ionophore ionomycin prompted significant mitochondrial Ca(2) (+) uptake in neurons with fragmented mitochondria, indicating that fragmentation did not prevent mitochondrial Ca(2) (+) uptake but presumably decreased the functional coupling between RyR-mediated Ca(2) (+) release and the mitochondrial Ca(2) (+) uniporter. Taken together, our results indicate that stimulation of redox-sensitive RyR-mediated Ca(2) (+) release by iron causes significant neuronal mitochondrial fragmentation, which presumably contributes to the impairment of neuronal function produced by iron accumulation.<\/p>\n\n\n\n<p><a href=\"https:\/\/doi.org\/10.3389\/fnmol.2014.00013\">https:\/\/doi.org\/10.3389\/fnmol.2014.00013<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>SanMart\u00edn, C. D., Paula-Lima, A. C., Garc\u00eda, A., Barattini, P., Hartel, S., N\u00fa\u00f1ez, M. T., &#038; Hidalgo, C. (2014). Ryanodine receptor-mediated Ca2+ release underlies iron-induced mitochondrial fission and stimulates mitochondrial Ca2+ uptake in primary hippocampal neurons. Frontiers in molecular neuroscience, 7, 13.<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_kadence_starter_templates_imported_post":false,"_kad_post_transparent":"","_kad_post_title":"","_kad_post_layout":"","_kad_post_sidebar_id":"","_kad_post_content_style":"","_kad_post_vertical_padding":"","_kad_post_feature":"","_kad_post_feature_position":"","_kad_post_header":false,"_kad_post_footer":false,"_kad_post_classname":"","footnotes":""},"categories":[28],"tags":[],"class_list":["post-2493","post","type-post","status-publish","format-standard","hentry","category-publicatios-2014"],"_links":{"self":[{"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/posts\/2493","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/comments?post=2493"}],"version-history":[{"count":4,"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/posts\/2493\/revisions"}],"predecessor-version":[{"id":4196,"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/posts\/2493\/revisions\/4196"}],"wp:attachment":[{"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/media?parent=2493"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/categories?post=2493"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scian.cl\/scientific-image-analysis\/wp-json\/wp\/v2\/tags?post=2493"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}