AMPK‐mediated degradation of Nav1.5 through autophagy
ABSTRACTThe voltage‐gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat ca...
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| Veröffentlicht in: | The FASEB journal 2019-04, Vol.33 (4), p.5366-5376 |
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| creator | Liu, Xuehua Chen, Zheng Han, Zhonglin Liu, Yu Wu, Xiang Peng, Yuzhu Di, Wencheng Lan, Rongfang Sun, Bugao Xu, Biao Xu, Wei |
| description | ABSTRACTThe voltage‐gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down‐regulated by AMPK‐mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule‐associated protein 1 light chain 3 (LC3), by exposing the LC3‐interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.—Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. AMPK‐mediated degradation of Nav1.5 through autophagy. FASEB J. 33, 5366–5376 (2019). www.fasebj.org |
| doi_str_mv | 10.1096/fj.201801583RR |
| format | Article |
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However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down‐regulated by AMPK‐mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule‐associated protein 1 light chain 3 (LC3), by exposing the LC3‐interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.—Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. AMPK‐mediated degradation of Nav1.5 through autophagy. FASEB J. 33, 5366–5376 (2019). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.201801583RR</identifier><identifier>PMID: 30759345</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>AMP-Activated Protein Kinases - metabolism ; Animals ; Animals, Newborn ; Autophagy - physiology ; Immunoprecipitation ; ischemia and reperfusion injury ; Male ; Muscle Cells - metabolism ; Myocytes, Cardiac - metabolism ; NAV1.5 Voltage-Gated Sodium Channel - metabolism ; Phosphorylation ; protein degradation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; SCN5A ; Signal Transduction ; sodium channel</subject><ispartof>The FASEB journal, 2019-04, Vol.33 (4), p.5366-5376</ispartof><rights>FASEB</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389R-3b8aa3c0f84d1ed4f4f27631dad3fff84d326b93018a241e8eaf57a76829d47c3</citedby><cites>FETCH-LOGICAL-c389R-3b8aa3c0f84d1ed4f4f27631dad3fff84d326b93018a241e8eaf57a76829d47c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.201801583RR$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.201801583RR$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30759345$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Xuehua</creatorcontrib><creatorcontrib>Chen, Zheng</creatorcontrib><creatorcontrib>Han, Zhonglin</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Wu, Xiang</creatorcontrib><creatorcontrib>Peng, Yuzhu</creatorcontrib><creatorcontrib>Di, Wencheng</creatorcontrib><creatorcontrib>Lan, Rongfang</creatorcontrib><creatorcontrib>Sun, Bugao</creatorcontrib><creatorcontrib>Xu, Biao</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><title>AMPK‐mediated degradation of Nav1.5 through autophagy</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACTThe voltage‐gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down‐regulated by AMPK‐mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule‐associated protein 1 light chain 3 (LC3), by exposing the LC3‐interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.—Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. AMPK‐mediated degradation of Nav1.5 through autophagy. FASEB J. 33, 5366–5376 (2019). www.fasebj.org</description><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Autophagy - physiology</subject><subject>Immunoprecipitation</subject><subject>ischemia and reperfusion injury</subject><subject>Male</subject><subject>Muscle Cells - metabolism</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>NAV1.5 Voltage-Gated Sodium Channel - metabolism</subject><subject>Phosphorylation</subject><subject>protein degradation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>SCN5A</subject><subject>Signal Transduction</subject><subject>sodium channel</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1OwzAQhC0EoqVw5Yhy5JKwthPbOXAoFeWv_KjA2XJju02VNsVOQL3xCDwjT0KqFtQb0korrb6Z1QxCxxgiDCk7s9OIABaAE0GHwx3UxgmFkAkGu6gNIiUhY1S00IH3UwDAgNk-alHgSUrjpI149_7p7vvza2Z0riqjA23GTmlV5eU8KG3woN5xlATVxJX1eBKouioXEzVeHqI9qwpvjja7g177ly-963DweHXT6w7CjIp0GNKRUIpmYEWssdGxjS3hjGKtNLV2daWEjVLaRFAkxkYYZROuOBMk1THPaAedrn0Xrnyrja_kLPeZKQo1N2XtJSEAnK-mQaM1mrnSe2esXLh8ptxSYpCrsqSdyq2yGsHJxrseNfn_8N92GuB8DXzkhVn-Yyf7zxekf7v94Ad3gXaL</recordid><startdate>201904</startdate><enddate>201904</enddate><creator>Liu, Xuehua</creator><creator>Chen, Zheng</creator><creator>Han, Zhonglin</creator><creator>Liu, Yu</creator><creator>Wu, Xiang</creator><creator>Peng, Yuzhu</creator><creator>Di, Wencheng</creator><creator>Lan, Rongfang</creator><creator>Sun, Bugao</creator><creator>Xu, Biao</creator><creator>Xu, Wei</creator><general>Federation of American Societies for Experimental Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201904</creationdate><title>AMPK‐mediated degradation of Nav1.5 through autophagy</title><author>Liu, Xuehua ; Chen, Zheng ; Han, Zhonglin ; Liu, Yu ; Wu, Xiang ; Peng, Yuzhu ; Di, Wencheng ; Lan, Rongfang ; Sun, Bugao ; Xu, Biao ; Xu, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389R-3b8aa3c0f84d1ed4f4f27631dad3fff84d326b93018a241e8eaf57a76829d47c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Autophagy - physiology</topic><topic>Immunoprecipitation</topic><topic>ischemia and reperfusion injury</topic><topic>Male</topic><topic>Muscle Cells - metabolism</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>NAV1.5 Voltage-Gated Sodium Channel - metabolism</topic><topic>Phosphorylation</topic><topic>protein degradation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>SCN5A</topic><topic>Signal Transduction</topic><topic>sodium channel</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Xuehua</creatorcontrib><creatorcontrib>Chen, Zheng</creatorcontrib><creatorcontrib>Han, Zhonglin</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Wu, Xiang</creatorcontrib><creatorcontrib>Peng, Yuzhu</creatorcontrib><creatorcontrib>Di, Wencheng</creatorcontrib><creatorcontrib>Lan, Rongfang</creatorcontrib><creatorcontrib>Sun, Bugao</creatorcontrib><creatorcontrib>Xu, Biao</creatorcontrib><creatorcontrib>Xu, Wei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Xuehua</au><au>Chen, Zheng</au><au>Han, Zhonglin</au><au>Liu, Yu</au><au>Wu, Xiang</au><au>Peng, Yuzhu</au><au>Di, Wencheng</au><au>Lan, Rongfang</au><au>Sun, Bugao</au><au>Xu, Biao</au><au>Xu, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AMPK‐mediated degradation of Nav1.5 through autophagy</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2019-04</date><risdate>2019</risdate><volume>33</volume><issue>4</issue><spage>5366</spage><epage>5376</epage><pages>5366-5376</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACTThe voltage‐gated cardiac sodium channel, Nav1.5, is the key component that controls cardiac excitative electrical impulse and propagation. However, the dynamic alterations of Nav1.5 during cardiac ischemia and reperfusion (I/R) are seldom reported. We found that the protein levels of rat cardiac Nav1.5 were significantly decreased in response to cardiac I/R injury. By simulating I/R injury in cells through activating AMPK by glucose deprivation, AMPK activator treatment, or hypoxia and reoxygenation (H/R), we found that Nav1.5 was down‐regulated by AMPK‐mediated autophagic degradation. Furthermore, AMPK was found to phosphorylate Nav1.5 at threonine (T) 101, which then regulates the interaction between Nav1.5 and the autophagic adaptor protein, microtubule‐associated protein 1 light chain 3 (LC3), by exposing the LC3‐interacting region adjacent to T101 in Nav1.5. This study highlights an instrumental role of AMPK in mediating the autophagic degradation of Nav1.5 during cardiac I/R injury.—Liu, X., Chen, Z., Han, Z., Liu, Y., Wu, X., Peng, Y., Di, W., Lan, R., Sun, B., Xu, B., Xu, W. 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| subjects | AMP-Activated Protein Kinases - metabolism Animals Animals, Newborn Autophagy - physiology Immunoprecipitation ischemia and reperfusion injury Male Muscle Cells - metabolism Myocytes, Cardiac - metabolism NAV1.5 Voltage-Gated Sodium Channel - metabolism Phosphorylation protein degradation Rats Rats, Sprague-Dawley Reperfusion Injury - metabolism Reverse Transcriptase Polymerase Chain Reaction SCN5A Signal Transduction sodium channel |
| title | AMPK‐mediated degradation of Nav1.5 through autophagy |
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