Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes
Background: Intracellular uric acid is known to increase the protein level and channel current of atrial Kv1.5; however, mechanisms of the uric acid-induced enhancement of Kv1.5 expression remain unclear. Methods and Results: The effects of uric acid on mRNA and protein levels of Kv1.5, as well as t...
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| Veröffentlicht in: | Circulation Journal 2019/03/25, Vol.83(4), pp.718-726 |
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| creator | Taufiq, Fikri Maharani, Nani Li, Peili Kurata, Yasutaka Ikeda, Nobuhito Kuwabara, Masanari Otani, Naoyuki Miake, Junichiro Hasegawa, Akira Tsuneto, Motokazu Shirayoshi, Yasuaki Ninomiya, Haruaki Saitoh, Tatsuya Nakai, Akira Yamamoto, Kazuhiro Hisatome, Ichiro |
| description | Background: Intracellular uric acid is known to increase the protein level and channel current of atrial Kv1.5; however, mechanisms of the uric acid-induced enhancement of Kv1.5 expression remain unclear. Methods and Results: The effects of uric acid on mRNA and protein levels of Kv1.5, as well as those of Akt, HSF1 and Hsp70, in HL-1 cardiomyocytes were studied by using qRT-PCR and Western blotting. The uptake of uric acid was measured using radio-labeled uric acid. The Kv1.5-mediated channel current was also measured by using patch clamp techniques. Uric acid up-taken by HL-1 cells significantly increased the level of Kv1.5 proteins in a concentration-dependent manner, with this increase abolished by an uric acid transporter inhibitor. Uric acid slowed degradation of Kv1.5 proteins without altering its mRNA level. Uric acid enhanced phosphorylation of Akt and HSF1, and thereby increased both transcription and translation of Hsp70; these effects were abolished by a PI3K inhibitor. Hsp70 knockdown abolished the uric acid-induced increases of Kv1.5 proteins and channel currents. Conclusions: Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70. |
| doi_str_mv | 10.1253/circj.CJ-18-1088 |
| format | Article |
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Methods and Results: The effects of uric acid on mRNA and protein levels of Kv1.5, as well as those of Akt, HSF1 and Hsp70, in HL-1 cardiomyocytes were studied by using qRT-PCR and Western blotting. The uptake of uric acid was measured using radio-labeled uric acid. The Kv1.5-mediated channel current was also measured by using patch clamp techniques. Uric acid up-taken by HL-1 cells significantly increased the level of Kv1.5 proteins in a concentration-dependent manner, with this increase abolished by an uric acid transporter inhibitor. Uric acid slowed degradation of Kv1.5 proteins without altering its mRNA level. Uric acid enhanced phosphorylation of Akt and HSF1, and thereby increased both transcription and translation of Hsp70; these effects were abolished by a PI3K inhibitor. Hsp70 knockdown abolished the uric acid-induced increases of Kv1.5 proteins and channel currents. Conclusions: Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70.</description><identifier>ISSN: 1346-9843</identifier><identifier>ISSN: 1347-4820</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-18-1088</identifier><identifier>PMID: 30787218</identifier><language>eng</language><publisher>Japan: The Japanese Circulation Society</publisher><subject>Akt ; Animals ; Cell Line ; Heat shock factor 1 ; Heat shock protein 70 ; Heat Shock Transcription Factors - metabolism ; HSP70 Heat-Shock Proteins - metabolism ; Kv1.5 ; Kv1.5 Potassium Channel - drug effects ; Kv1.5 Potassium Channel - metabolism ; Mice ; Myocytes, Cardiac - metabolism ; Phosphorylation - drug effects ; Protein Biosynthesis ; Proto-Oncogene Proteins c-akt - metabolism ; Transcription, Genetic ; Uric acid ; Uric Acid - pharmacology</subject><ispartof>Circulation Journal, 2019/03/25, Vol.83(4), pp.718-726</ispartof><rights>2019 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c706t-99f721805b6db124adeeb0f91b2aac528c3181aba89de16b069e412a62da4c753</citedby><cites>FETCH-LOGICAL-c706t-99f721805b6db124adeeb0f91b2aac528c3181aba89de16b069e412a62da4c753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30787218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taufiq, Fikri</creatorcontrib><creatorcontrib>Maharani, Nani</creatorcontrib><creatorcontrib>Li, Peili</creatorcontrib><creatorcontrib>Kurata, Yasutaka</creatorcontrib><creatorcontrib>Ikeda, Nobuhito</creatorcontrib><creatorcontrib>Kuwabara, Masanari</creatorcontrib><creatorcontrib>Otani, Naoyuki</creatorcontrib><creatorcontrib>Miake, Junichiro</creatorcontrib><creatorcontrib>Hasegawa, Akira</creatorcontrib><creatorcontrib>Tsuneto, Motokazu</creatorcontrib><creatorcontrib>Shirayoshi, Yasuaki</creatorcontrib><creatorcontrib>Ninomiya, Haruaki</creatorcontrib><creatorcontrib>Saitoh, Tatsuya</creatorcontrib><creatorcontrib>Nakai, Akira</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiro</creatorcontrib><creatorcontrib>Hisatome, Ichiro</creatorcontrib><title>Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes</title><title>Circulation Journal</title><addtitle>Circ J</addtitle><description>Background: Intracellular uric acid is known to increase the protein level and channel current of atrial Kv1.5; however, mechanisms of the uric acid-induced enhancement of Kv1.5 expression remain unclear. Methods and Results: The effects of uric acid on mRNA and protein levels of Kv1.5, as well as those of Akt, HSF1 and Hsp70, in HL-1 cardiomyocytes were studied by using qRT-PCR and Western blotting. The uptake of uric acid was measured using radio-labeled uric acid. The Kv1.5-mediated channel current was also measured by using patch clamp techniques. Uric acid up-taken by HL-1 cells significantly increased the level of Kv1.5 proteins in a concentration-dependent manner, with this increase abolished by an uric acid transporter inhibitor. Uric acid slowed degradation of Kv1.5 proteins without altering its mRNA level. Uric acid enhanced phosphorylation of Akt and HSF1, and thereby increased both transcription and translation of Hsp70; these effects were abolished by a PI3K inhibitor. Hsp70 knockdown abolished the uric acid-induced increases of Kv1.5 proteins and channel currents. Conclusions: Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70.</description><subject>Akt</subject><subject>Animals</subject><subject>Cell Line</subject><subject>Heat shock factor 1</subject><subject>Heat shock protein 70</subject><subject>Heat Shock Transcription Factors - metabolism</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>Kv1.5</subject><subject>Kv1.5 Potassium Channel - drug effects</subject><subject>Kv1.5 Potassium Channel - metabolism</subject><subject>Mice</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Biosynthesis</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Transcription, Genetic</subject><subject>Uric acid</subject><subject>Uric Acid - pharmacology</subject><issn>1346-9843</issn><issn>1347-4820</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkD1v2zAQhoWiQZOm3TsVHLvQIakvajQEO07qIAHSzMSJPNV0Zcolabf6A_3dlWMnWe5ueN4HhzdJvnA24SJPr7T1ej2pbymXlDMp3yUXPM1KmknB3j_fBa1klp4nH0NYMyYqllcfkvOUlbIUXF4k_5681WSqraE3zuw0GjJzK3AaN-hiIH1Lvu_5JCcPvo9oHZn93XoMwfaOgDOkHlmH3WiIdm_jQPYWSFwhmf6KdPE453QRtiUjDxBXf2Ago2GxpJxMo7fQkbuh10PE8Ck5a6EL-Pm0L5On-exHvaDL--uberqkumRFpFXVHt5meVOYhosMDGLD2oo3AkDnQuqUSw4NyMogLxpWVJhxAYUwkOkyTy-Tb0fv1ve_dxii2tigsevAYb8LapRno6YsihFlR1T7PgSPrdp6uwE_KM7UoX313L6qbxWX6tD-GPl6su-aDZrXwEvdIzA_AusQ4Se-AuCj1R2ejDJV2WG8md-AFXiFLv0PXAeZ2g</recordid><startdate>20190325</startdate><enddate>20190325</enddate><creator>Taufiq, Fikri</creator><creator>Maharani, Nani</creator><creator>Li, Peili</creator><creator>Kurata, Yasutaka</creator><creator>Ikeda, Nobuhito</creator><creator>Kuwabara, Masanari</creator><creator>Otani, Naoyuki</creator><creator>Miake, Junichiro</creator><creator>Hasegawa, Akira</creator><creator>Tsuneto, Motokazu</creator><creator>Shirayoshi, Yasuaki</creator><creator>Ninomiya, Haruaki</creator><creator>Saitoh, Tatsuya</creator><creator>Nakai, Akira</creator><creator>Yamamoto, Kazuhiro</creator><creator>Hisatome, Ichiro</creator><general>The Japanese Circulation Society</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>20190325</creationdate><title>Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes</title><author>Taufiq, Fikri ; Maharani, Nani ; Li, Peili ; Kurata, Yasutaka ; Ikeda, Nobuhito ; Kuwabara, Masanari ; Otani, Naoyuki ; Miake, Junichiro ; Hasegawa, Akira ; Tsuneto, Motokazu ; Shirayoshi, Yasuaki ; Ninomiya, Haruaki ; Saitoh, Tatsuya ; Nakai, Akira ; Yamamoto, Kazuhiro ; Hisatome, Ichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c706t-99f721805b6db124adeeb0f91b2aac528c3181aba89de16b069e412a62da4c753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Akt</topic><topic>Animals</topic><topic>Cell Line</topic><topic>Heat shock factor 1</topic><topic>Heat shock protein 70</topic><topic>Heat Shock Transcription Factors - metabolism</topic><topic>HSP70 Heat-Shock Proteins - metabolism</topic><topic>Kv1.5</topic><topic>Kv1.5 Potassium Channel - drug effects</topic><topic>Kv1.5 Potassium Channel - metabolism</topic><topic>Mice</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Biosynthesis</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Transcription, Genetic</topic><topic>Uric acid</topic><topic>Uric Acid - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taufiq, Fikri</creatorcontrib><creatorcontrib>Maharani, Nani</creatorcontrib><creatorcontrib>Li, Peili</creatorcontrib><creatorcontrib>Kurata, Yasutaka</creatorcontrib><creatorcontrib>Ikeda, Nobuhito</creatorcontrib><creatorcontrib>Kuwabara, Masanari</creatorcontrib><creatorcontrib>Otani, Naoyuki</creatorcontrib><creatorcontrib>Miake, Junichiro</creatorcontrib><creatorcontrib>Hasegawa, Akira</creatorcontrib><creatorcontrib>Tsuneto, Motokazu</creatorcontrib><creatorcontrib>Shirayoshi, Yasuaki</creatorcontrib><creatorcontrib>Ninomiya, Haruaki</creatorcontrib><creatorcontrib>Saitoh, Tatsuya</creatorcontrib><creatorcontrib>Nakai, Akira</creatorcontrib><creatorcontrib>Yamamoto, Kazuhiro</creatorcontrib><creatorcontrib>Hisatome, Ichiro</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>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taufiq, Fikri</au><au>Maharani, Nani</au><au>Li, Peili</au><au>Kurata, Yasutaka</au><au>Ikeda, Nobuhito</au><au>Kuwabara, Masanari</au><au>Otani, Naoyuki</au><au>Miake, Junichiro</au><au>Hasegawa, Akira</au><au>Tsuneto, Motokazu</au><au>Shirayoshi, Yasuaki</au><au>Ninomiya, Haruaki</au><au>Saitoh, Tatsuya</au><au>Nakai, Akira</au><au>Yamamoto, Kazuhiro</au><au>Hisatome, Ichiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2019-03-25</date><risdate>2019</risdate><volume>83</volume><issue>4</issue><spage>718</spage><epage>726</epage><pages>718-726</pages><issn>1346-9843</issn><issn>1347-4820</issn><eissn>1347-4820</eissn><abstract>Background: Intracellular uric acid is known to increase the protein level and channel current of atrial Kv1.5; however, mechanisms of the uric acid-induced enhancement of Kv1.5 expression remain unclear. Methods and Results: The effects of uric acid on mRNA and protein levels of Kv1.5, as well as those of Akt, HSF1 and Hsp70, in HL-1 cardiomyocytes were studied by using qRT-PCR and Western blotting. The uptake of uric acid was measured using radio-labeled uric acid. The Kv1.5-mediated channel current was also measured by using patch clamp techniques. Uric acid up-taken by HL-1 cells significantly increased the level of Kv1.5 proteins in a concentration-dependent manner, with this increase abolished by an uric acid transporter inhibitor. Uric acid slowed degradation of Kv1.5 proteins without altering its mRNA level. Uric acid enhanced phosphorylation of Akt and HSF1, and thereby increased both transcription and translation of Hsp70; these effects were abolished by a PI3K inhibitor. Hsp70 knockdown abolished the uric acid-induced increases of Kv1.5 proteins and channel currents. Conclusions: Intracellular uric acid could stabilize Kv1.5 proteins through phosphorylation of Akt and HSF1 leading to enhanced expression of Hsp70.</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>30787218</pmid><doi>10.1253/circj.CJ-18-1088</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Akt Animals Cell Line Heat shock factor 1 Heat shock protein 70 Heat Shock Transcription Factors - metabolism HSP70 Heat-Shock Proteins - metabolism Kv1.5 Kv1.5 Potassium Channel - drug effects Kv1.5 Potassium Channel - metabolism Mice Myocytes, Cardiac - metabolism Phosphorylation - drug effects Protein Biosynthesis Proto-Oncogene Proteins c-akt - metabolism Transcription, Genetic Uric acid Uric Acid - pharmacology |
| title | Uric Acid-Induced Enhancements of Kv1.5 Protein Expression and Channel Activity via the Akt-HSF1-Hsp70 Pathway in HL-1 Atrial Myocytes |
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