H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation
Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2017-01, Vol.483 (1), p.534-540 |
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| creator | Lu, Guihua Xu, Chenggui Tang, Kaiyu Zhang, Juhong Li, Qinglang Peng, Longyun Wang, Yesong Huang, Zhibin Gao, Xiuren |
| description | Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression.
•Mechanisms of H2S-related downregulation of atrial Kv1.5 channel during AF.•H2S-induced inhibition of atrial Ang II upregulation and ROS production are involved.•H2S decreases Kv1.5 by inactivation of Nox4-related P-Smad2/3 and P-ERK 1/2 signaling. |
| doi_str_mv | 10.1016/j.bbrc.2016.12.110 |
| format | Article |
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•Mechanisms of H2S-related downregulation of atrial Kv1.5 channel during AF.•H2S-induced inhibition of atrial Ang II upregulation and ROS production are involved.•H2S decreases Kv1.5 by inactivation of Nox4-related P-Smad2/3 and P-ERK 1/2 signaling.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2016.12.110</identifier><language>eng</language><publisher>Elsevier Inc</publisher><subject>Angiotensin II ; Atrial fibrillation ; Hydrogen sulfide ; Kv1.5 ; Reactive oxygen species</subject><ispartof>Biochemical and biophysical research communications, 2017-01, Vol.483 (1), p.534-540</ispartof><rights>2016 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2016.12.110$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids></links><search><creatorcontrib>Lu, Guihua</creatorcontrib><creatorcontrib>Xu, Chenggui</creatorcontrib><creatorcontrib>Tang, Kaiyu</creatorcontrib><creatorcontrib>Zhang, Juhong</creatorcontrib><creatorcontrib>Li, Qinglang</creatorcontrib><creatorcontrib>Peng, Longyun</creatorcontrib><creatorcontrib>Wang, Yesong</creatorcontrib><creatorcontrib>Huang, Zhibin</creatorcontrib><creatorcontrib>Gao, Xiuren</creatorcontrib><title>H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation</title><title>Biochemical and biophysical research communications</title><description>Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression.
•Mechanisms of H2S-related downregulation of atrial Kv1.5 channel during AF.•H2S-induced inhibition of atrial Ang II upregulation and ROS production are involved.•H2S decreases Kv1.5 by inactivation of Nox4-related P-Smad2/3 and P-ERK 1/2 signaling.</description><subject>Angiotensin II</subject><subject>Atrial fibrillation</subject><subject>Hydrogen sulfide</subject><subject>Kv1.5</subject><subject>Reactive oxygen species</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNotkE9LAzEQxYMoWKtfwFOOXnbNZLN_Cl6kqC0WC1bBW0g2szWlzdZkt-jdD26WepoZ5s2bx4-Qa2ApMChuN6nWvk557FPgKQA7ISNgE5ZwYOKUjBhjRcIn8HFOLkLYMAYgismI_M74ilr3abXtAlVubdsOXbCOzueJdaav0VDVeau29PkAaU77vcd1v1WdbR3VP3EZD_o4ujV9ab9FskNjVRfPXpcrukaH_qg1vR80_2aN1d5ujzaX5KxR24BX_3VM3h8f3qazZLF8mk_vFwlyAV3SYCPKrNaVbhjmmYEcmM5Q1CKHqmAGGqiNrnLBs0pNWC5AcVU0TWlKrkVZZmNyc_Td-_arx9DJnQ01xhQO2z5IqHJeVvEHROndUYoxz8Gil6G26CIN67HupGmtBCYH-HIjB_hygC-Bywg_-wPcAHtY</recordid><startdate>20170129</startdate><enddate>20170129</enddate><creator>Lu, Guihua</creator><creator>Xu, Chenggui</creator><creator>Tang, Kaiyu</creator><creator>Zhang, Juhong</creator><creator>Li, Qinglang</creator><creator>Peng, Longyun</creator><creator>Wang, Yesong</creator><creator>Huang, Zhibin</creator><creator>Gao, Xiuren</creator><general>Elsevier Inc</general><scope>7X8</scope></search><sort><creationdate>20170129</creationdate><title>H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation</title><author>Lu, Guihua ; Xu, Chenggui ; Tang, Kaiyu ; Zhang, Juhong ; Li, Qinglang ; Peng, Longyun ; Wang, Yesong ; Huang, Zhibin ; Gao, Xiuren</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e241t-fef473cb8bf0e53d1510b3e4c451860d1f1cdb854238a90541a2a6ff7d72b4773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiotensin II</topic><topic>Atrial fibrillation</topic><topic>Hydrogen sulfide</topic><topic>Kv1.5</topic><topic>Reactive oxygen species</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Guihua</creatorcontrib><creatorcontrib>Xu, Chenggui</creatorcontrib><creatorcontrib>Tang, Kaiyu</creatorcontrib><creatorcontrib>Zhang, Juhong</creatorcontrib><creatorcontrib>Li, Qinglang</creatorcontrib><creatorcontrib>Peng, Longyun</creatorcontrib><creatorcontrib>Wang, Yesong</creatorcontrib><creatorcontrib>Huang, Zhibin</creatorcontrib><creatorcontrib>Gao, Xiuren</creatorcontrib><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Guihua</au><au>Xu, Chenggui</au><au>Tang, Kaiyu</au><au>Zhang, Juhong</au><au>Li, Qinglang</au><au>Peng, Longyun</au><au>Wang, Yesong</au><au>Huang, Zhibin</au><au>Gao, Xiuren</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation</atitle><jtitle>Biochemical and biophysical research communications</jtitle><date>2017-01-29</date><risdate>2017</risdate><volume>483</volume><issue>1</issue><spage>534</spage><epage>540</epage><pages>534-540</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Our previous study demonstrated that angiotensin II (Ang II) upregulates the expression of Kv1.5, a promising target for atrial fibrillation (AF) therapy, by activating ROS-dependent P-Smad2/3 and P-ERK 1/2. A recent study showed that hydrogen sulfide (H2S) may modulate the effects of angiotensin II (Ang II) by inhibiting the NADPH oxidase 4 (Nox4)-ROS signaling in the heart. The present study aimed to determine whether H2S is involved in the regulation of atrial Kv1.5 via ROS-related mechanisms in AF. Cultured neonatal rat atrial myocytes and a beagle model of AF were used for this study. In the neonatal rat atrial myocytes, quantitative PCR and enzyme immunoassays revealed that the mRNA expression levels of angiotensinogen, angiotensin-converting enzyme, and Ang II type I receptor (AT1R) and the Ang II supernatant concentration were significantly increased by hydrogen peroxide (H2O2) incubation, and these H2O2-induced alterations were reversed by diphenyleneiodonium, apocynin and H2S supplementation. Flow cytometry and Western blotting revealed that blockade of H2S biosynthesis using dl-propargylglycine increased ROS production and the expression of Ang II and Kv1.5. Sodium hydrosulfide (an exogenous H2S donor) and Nox4 siRNA inhibited Ang II-induced ROS production and Ang II-induced expression of Kv1.5, P-Smad2/3, P-ERK 1/2. Sodium hydrosulfide suppressed the Ang II-induced upregulation of Nox4. In our beagle AF model, 24 h of rapid atrial pacing (RAP) increased the atrial Ang II concentration, ROS production and the protein expression of Nox4, Kv1.5, P-Smad2/3 and P-ERK 1/2. These RAP-induced changes were inhibited by H2S supplementation and losartan (an AT1R blocker) pretreatment. In conclusion, our study indicates that H2S downregulates Ang II-induced atrial Kv1.5 expression by attenuating Nox4-related ROS-triggered P-Smad2/3 and P-ERK 1/2 activation during AF. H2S supplementation would be beneficial for AF treatment via the suppression of atrial Kv1.5 expression.
•Mechanisms of H2S-related downregulation of atrial Kv1.5 channel during AF.•H2S-induced inhibition of atrial Ang II upregulation and ROS production are involved.•H2S decreases Kv1.5 by inactivation of Nox4-related P-Smad2/3 and P-ERK 1/2 signaling.</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.bbrc.2016.12.110</doi><tpages>7</tpages></addata></record> |
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| subjects | Angiotensin II Atrial fibrillation Hydrogen sulfide Kv1.5 Reactive oxygen species |
| title | H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4-mediated ROS generation during atrial fibrillation |
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