Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury
Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an importan...
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| creator | Liu, Baoshan Wang, Jiali Li, Minghua Yuan, Qiuhuan Xue, Mengyang Xu, Feng Chen, Yuguo |
| description | Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P |
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Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.14297</identifier><identifier>PMID: 28038474</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Acetylglucosamine - metabolism ; Aldehyde Dehydrogenase - chemistry ; Aldehyde Dehydrogenase - metabolism ; Animals ; Apoptosis ; Cell Proliferation ; Cells, Cultured ; Glycosylation ; Humans ; Hyperglycemia - enzymology ; Hyperglycemia - etiology ; Hyperglycemia - pathology ; Male ; Myocardial Reperfusion Injury - complications ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - enzymology ; Myocytes, Cardiac - pathology ; Protein Processing, Post-Translational ; Rats ; Rats, Wistar ; Research Paper</subject><ispartof>Oncotarget, 2017-03, Vol.8 (12), p.19413-19426</ispartof><rights>Copyright: © 2017 Liu et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-dec0be1193588586ec378d65a5fcf96a2468f2f874411dbc196ecb14752ab6e43</citedby><cites>FETCH-LOGICAL-c356t-dec0be1193588586ec378d65a5fcf96a2468f2f874411dbc196ecb14752ab6e43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386694/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386694/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28038474$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Baoshan</creatorcontrib><creatorcontrib>Wang, Jiali</creatorcontrib><creatorcontrib>Li, Minghua</creatorcontrib><creatorcontrib>Yuan, Qiuhuan</creatorcontrib><creatorcontrib>Xue, Mengyang</creatorcontrib><creatorcontrib>Xu, Feng</creatorcontrib><creatorcontrib>Chen, Yuguo</creatorcontrib><title>Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection.</description><subject>Acetylglucosamine - metabolism</subject><subject>Aldehyde Dehydrogenase - chemistry</subject><subject>Aldehyde Dehydrogenase - metabolism</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Hyperglycemia - enzymology</subject><subject>Hyperglycemia - etiology</subject><subject>Hyperglycemia - pathology</subject><subject>Male</subject><subject>Myocardial Reperfusion Injury - complications</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - enzymology</subject><subject>Myocytes, Cardiac - pathology</subject><subject>Protein Processing, Post-Translational</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Research Paper</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUtP3TAQha2qqCDgB3RTedlNIH7G2SBd0fKQrsoG1pbtTG6MkvhiO1Wz4bcTLs_OxiPNd854dBD6TsoToiSjp2F0IZu4gXxCOK2rL-iA1LwuqBDs66d-Hx2ndF8uJXilaP0N7VNVMsUrfoAer8fOW599GHFo8Wr964piO-Ob4rJ3f1Zu7s1u5sKYo7dThoRzwLkD3M1biJt-djB4h-GfcRCteXMa5uBMbLzpsU-uWxhzGmFRtFN6Rvx4P8X5CO21pk9w_PoeoruL37fnV8X65vL6fLUuHBMyFw240gIhNRNKCSXBsUo1UhjRuraWhnKpWtqqinNCGutIvSCW8EpQYyVwdojOXny3kx2gcbBcY3q9jX4wcdbBeP3_ZPSd3oS_WjAlZf1s8PPVIIaHCVLWw3IW9L0ZIUxJEyW4JFJWckHJC-piSClC-76GlHoXnf6ITu-iWzQ_Pv_vXfEWFHsC-iabew</recordid><startdate>20170321</startdate><enddate>20170321</enddate><creator>Liu, Baoshan</creator><creator>Wang, Jiali</creator><creator>Li, Minghua</creator><creator>Yuan, Qiuhuan</creator><creator>Xue, Mengyang</creator><creator>Xu, Feng</creator><creator>Chen, Yuguo</creator><general>Impact Journals LLC</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><scope>5PM</scope></search><sort><creationdate>20170321</creationdate><title>Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury</title><author>Liu, Baoshan ; Wang, Jiali ; Li, Minghua ; Yuan, Qiuhuan ; Xue, Mengyang ; Xu, Feng ; Chen, Yuguo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-dec0be1193588586ec378d65a5fcf96a2468f2f874411dbc196ecb14752ab6e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetylglucosamine - metabolism</topic><topic>Aldehyde Dehydrogenase - chemistry</topic><topic>Aldehyde Dehydrogenase - metabolism</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Glycosylation</topic><topic>Humans</topic><topic>Hyperglycemia - enzymology</topic><topic>Hyperglycemia - etiology</topic><topic>Hyperglycemia - pathology</topic><topic>Male</topic><topic>Myocardial Reperfusion Injury - complications</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - enzymology</topic><topic>Myocytes, Cardiac - pathology</topic><topic>Protein Processing, Post-Translational</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Research Paper</topic><toplevel>online_resources</toplevel><creatorcontrib>Liu, Baoshan</creatorcontrib><creatorcontrib>Wang, Jiali</creatorcontrib><creatorcontrib>Li, Minghua</creatorcontrib><creatorcontrib>Yuan, Qiuhuan</creatorcontrib><creatorcontrib>Xue, Mengyang</creatorcontrib><creatorcontrib>Xu, Feng</creatorcontrib><creatorcontrib>Chen, Yuguo</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Baoshan</au><au>Wang, Jiali</au><au>Li, Minghua</au><au>Yuan, Qiuhuan</au><au>Xue, Mengyang</au><au>Xu, Feng</au><au>Chen, Yuguo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-03-21</date><risdate>2017</risdate><volume>8</volume><issue>12</issue><spage>19413</spage><epage>19426</epage><pages>19413-19426</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.05). ALDH2 O-GlcNAc modification was increased whereas its activity was decreased in AHG+I/R and DM+I/R rats. High glucose (HG, 30mmol/L) markedly increased ALDH2 O-GlcNAc modification compared with Con group (5mmol/L) (P<0.05). ALDH2 O-GlcNAc modification was increased by 62.9% in Con+PUGNAc group whereas it was decreased by 44.1% in Con+DON group compared with Con group (P<0.05). Accordingly, ALDH2 activity was decreased by 18.1% in Con+PUGNAc group whereas it was increased by 17.9% in Con+DON group. Moreover, DON decreased levels of 4-hydroxy-2-nonenal (4-HNE), aldehydes, protein carbonyl accumulation and apoptosis index compared with HG+H/R group (P<0.05). Alda-1, a specific activator of ALDH2, significantly decreased ALDH2 O-GlcNAc modification and improved infarct size, apoptosis index and cardiac dysfunction induced by I/R combined with hyperglycemia. These findings demonstrate that ALDH2 O-GlcNAc modification is a key mechanism for the hyperglycemic exacerbation of myocardial I/R injury and Alda-1 has therapeutic potential for inducing cardioprotection.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28038474</pmid><doi>10.18632/oncotarget.14297</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylglucosamine - metabolism Aldehyde Dehydrogenase - chemistry Aldehyde Dehydrogenase - metabolism Animals Apoptosis Cell Proliferation Cells, Cultured Glycosylation Humans Hyperglycemia - enzymology Hyperglycemia - etiology Hyperglycemia - pathology Male Myocardial Reperfusion Injury - complications Myocytes, Cardiac - drug effects Myocytes, Cardiac - enzymology Myocytes, Cardiac - pathology Protein Processing, Post-Translational Rats Rats, Wistar Research Paper |
| title | Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury |
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