{"id":355,"date":"2021-04-05T07:46:37","date_gmt":"2021-04-05T07:46:37","guid":{"rendered":"https:\/\/vinuni.edu.vn\/research\/?p=355"},"modified":"2022-09-05T07:47:36","modified_gmt":"2022-09-05T07:47:36","slug":"oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification","status":"publish","type":"post","link":"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/","title":{"rendered":"Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification"},"content":{"rendered":"<p>Abstract<\/p>\n<p>Hyperphosphatemia is the primary risk factor for vascular calcification, which is closely associated with cardiovascular morbidity and mortality. Recent evidence showed that oxidative stress by high inorganic phosphate (Pi) mediates calcific changes in vascular smooth muscle cells (VSMCs). However, intracellular signaling responsible for Pi-induced oxidative stress remains unclear. Here, we investigated molecular mechanisms of Pi-induced oxidative stress related with intracellular Ca<sup>2+<\/sup>\u00a0([Ca<sup>2+<\/sup>]<sub>i<\/sub>) disturbance, which is critical for calcification of VSMCs. VSMCs isolated from rat thoracic aorta or A7r5 cells were incubated with high Pi-containing medium. Extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin were activated by high Pi that was required for vascular calcification. High Pi upregulated expressions of type III sodium-phosphate cotransporters PiT-1 and -2 and stimulated their trafficking to the plasma membrane. Interestingly, high Pi increased [Ca<sup>2+<\/sup>]<sub>i<\/sub>\u00a0exclusively dependent on extracellular Na<sup>+<\/sup>\u00a0and Ca<sup>2+<\/sup>\u00a0as well as PiT-1\/2 abundance. Furthermore, high-Pi induced plasma membrane depolarization mediated by PiT-1\/2. Pretreatment with verapamil, as a voltage-gated Ca<sup>2+<\/sup>\u00a0channel (VGCC) blocker, inhibited Pi-induced [Ca<sup>2+<\/sup>]<sub>i<\/sub>\u00a0elevation, oxidative stress, ERK activation, and osteogenic differentiation. These protective effects were reiterated by extracellular Ca<sup>2+<\/sup>-free condition, intracellular Ca<sup>2+<\/sup>\u00a0chelation, or suppression of oxidative stress. Mitochondrial superoxide scavenger also effectively abrogated ERK activation and osteogenic differentiation of VSMCs by high Pi. Taking all these together, we suggest that high Pi activates depolarization-triggered Ca<sup>2+<\/sup>\u00a0influx via VGCC, and subsequent [Ca<sup>2+<\/sup>]<sub>i<\/sub>\u00a0increase elicits oxidative stress and osteogenic differentiation. PiT-1\/2 mediates Pi-induced [Ca<sup>2+<\/sup>]<sub>i<\/sub>\u00a0overload and oxidative stress but in turn, PiT-1\/2 is upregulated by consequences of these alterations.<\/p>\n<p>Authors: Nguyen, T.T. and other authors<\/p>\n<p>Read more about the article<a href=\"https:\/\/journals.physiology.org\/doi\/abs\/10.1152\/ajpheart.00305.2020\">\u00a0here<\/a><\/p>\n<p>Read more about the author\u2019s publications\u00a0<a href=\"https:\/\/vinuni.edu.vn\/people\/nguyen-thi-tuyet-md-phd\/\">here<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Abstract Hyperphosphatemia is the primary risk factor for vascular calcification, which is closely associated with cardiovascular morbidity and mortality. Recent evidence showed that oxidative stress by high inorganic phosphate (Pi) mediates calcific changes in vascular smooth muscle cells (VSMCs). However, intracellular signaling responsible for Pi-induced oxidative stress remains unclear. Here, we investigated molecular mechanisms of [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":356,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[3],"tags":[38],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v19.6.1 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification - Vinuni Research Website<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification - Vinuni Research Website\" \/>\n<meta property=\"og:description\" content=\"Abstract Hyperphosphatemia is the primary risk factor for vascular calcification, which is closely associated with cardiovascular morbidity and mortality. Recent evidence showed that oxidative stress by high inorganic phosphate (Pi) mediates calcific changes in vascular smooth muscle cells (VSMCs). However, intracellular signaling responsible for Pi-induced oxidative stress remains unclear. Here, we investigated molecular mechanisms of [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/\" \/>\n<meta property=\"og:site_name\" content=\"Vinuni Research Website\" \/>\n<meta property=\"article:published_time\" content=\"2021-04-05T07:46:37+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2022-09-05T07:47:36+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/vinuni.edu.vn\/research\/wp-content\/uploads\/2022\/09\/American-Journal-of-Physiology-Heart-and-Circulatory-Physiology-e1617707234350.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"612\" \/>\n\t<meta property=\"og:image:height\" content=\"380\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"phuong.ntn\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"phuong.ntn\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/\",\"url\":\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/\",\"name\":\"Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification - Vinuni Research Website\",\"isPartOf\":{\"@id\":\"https:\/\/vinuni.edu.vn\/research\/#website\"},\"datePublished\":\"2021-04-05T07:46:37+00:00\",\"dateModified\":\"2022-09-05T07:47:36+00:00\",\"author\":{\"@id\":\"https:\/\/vinuni.edu.vn\/research\/#\/schema\/person\/d19200a9f0488a2d6374d8641ee8c085\"},\"breadcrumb\":{\"@id\":\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/vinuni.edu.vn\/research\/#website\",\"url\":\"https:\/\/vinuni.edu.vn\/research\/\",\"name\":\"Vinuni Research Website\",\"description\":\"\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/vinuni.edu.vn\/research\/?s={search_term_string}\"},\"query-input\":\"required name=search_term_string\"}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\/\/vinuni.edu.vn\/research\/#\/schema\/person\/d19200a9f0488a2d6374d8641ee8c085\",\"name\":\"phuong.ntn\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/vinuni.edu.vn\/research\/#\/schema\/person\/image\/\",\"url\":\"https:\/\/secure.gravatar.com\/avatar\/678312306781d0830679d2c1a8a112f1?s=96&d=mm&r=g\",\"contentUrl\":\"https:\/\/secure.gravatar.com\/avatar\/678312306781d0830679d2c1a8a112f1?s=96&d=mm&r=g\",\"caption\":\"phuong.ntn\"}}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification - Vinuni Research Website","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/vinuni.edu.vn\/research\/oxidative-stress-by-ca2-overload-is-critical-for-phosphate-induced-vascular-calcification\/","og_locale":"en_US","og_type":"article","og_title":"Oxidative Stress by Ca2+ Overload is Critical for Phosphate-Induced Vascular Calcification - Vinuni Research Website","og_description":"Abstract Hyperphosphatemia is the primary risk factor for vascular calcification, which is closely associated with cardiovascular morbidity and mortality. 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