Impact of intracellular glyceraldehyde-derived advanced glycation end-products on human hepatocyte cell death
Hepatocyte cell death is a key feature of nonalcoholic steatohepatitis (NASH); however, the pathogenesis of NASH currently remains unclear. We aimed to investigate the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (GA-AGEs) on human hepatocyte cell death. The a...
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| Veröffentlicht in: | Scientific reports 2017-10, Vol.7 (1), p.14282-11, Article 14282 |
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| description | Hepatocyte cell death is a key feature of nonalcoholic steatohepatitis (NASH); however, the pathogenesis of NASH currently remains unclear. We aimed to investigate the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (GA-AGEs) on human hepatocyte cell death. The accumulation of intracellular GA-AGEs has been associated with the induction of DNA damage and hepatocyte necrotic cell death. Among intracellular GA-AGEs, caspase-3 has been identified as a GA-AGE-modified protein with abrogated protein function. Furthermore, the activation of caspase-3 and induction of hepatocyte apoptosis by camptothecin, a DNA-damaging agent, was suppressed by a treatment with GA. These results suggest the inhibitory effects of GA-AGE-modified caspase-3 on the induction of DNA-damage-induced apoptosis, which is associated with hepatocyte necrosis. Therefore, the suppression of necrosis, the inflammatory form of cell death, by the accumulation of GA-AGEs and GA-AGE-modified caspase-3 may represent a novel therapeutic target for the pathogenesis of NASH. |
| doi_str_mv | 10.1038/s41598-017-14711-3 |
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We aimed to investigate the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (GA-AGEs) on human hepatocyte cell death. The accumulation of intracellular GA-AGEs has been associated with the induction of DNA damage and hepatocyte necrotic cell death. Among intracellular GA-AGEs, caspase-3 has been identified as a GA-AGE-modified protein with abrogated protein function. Furthermore, the activation of caspase-3 and induction of hepatocyte apoptosis by camptothecin, a DNA-damaging agent, was suppressed by a treatment with GA. These results suggest the inhibitory effects of GA-AGE-modified caspase-3 on the induction of DNA-damage-induced apoptosis, which is associated with hepatocyte necrosis. Therefore, the suppression of necrosis, the inflammatory form of cell death, by the accumulation of GA-AGEs and GA-AGE-modified caspase-3 may represent a novel therapeutic target for the pathogenesis of NASH.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-017-14711-3</identifier><identifier>PMID: 29079763</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 14/1 ; 14/34 ; 631/80/82 ; 692/4020/4021 ; Advanced glycosylation end products ; Apoptosis ; Camptothecin ; Caspase ; Caspase 3 - metabolism ; Caspase-3 ; Cell death ; Cell Death - drug effects ; Cell Death - physiology ; Deoxyribonucleic acid ; DNA ; DNA damage ; DNA Damage - drug effects ; DNA Damage - physiology ; Gangrene ; Glycation End Products, Advanced - administration & dosage ; Glycation End Products, Advanced - metabolism ; Glyceraldehyde ; Glyceraldehyde - administration & dosage ; Glyceraldehyde - metabolism ; Glycosylation ; Hep G2 Cells ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Hepatocytes - pathology ; Humanities and Social Sciences ; Humans ; Inflammation ; Intracellular ; Intracellular Space - drug effects ; Intracellular Space - metabolism ; Mortality ; multidisciplinary ; Necrosis ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - metabolism ; Pathogenesis ; Protective Agents - administration & dosage ; Science ; Science (multidisciplinary)</subject><ispartof>Scientific reports, 2017-10, Vol.7 (1), p.14282-11, Article 14282</ispartof><rights>The Author(s) 2017</rights><rights>2017. 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We aimed to investigate the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (GA-AGEs) on human hepatocyte cell death. The accumulation of intracellular GA-AGEs has been associated with the induction of DNA damage and hepatocyte necrotic cell death. Among intracellular GA-AGEs, caspase-3 has been identified as a GA-AGE-modified protein with abrogated protein function. Furthermore, the activation of caspase-3 and induction of hepatocyte apoptosis by camptothecin, a DNA-damaging agent, was suppressed by a treatment with GA. These results suggest the inhibitory effects of GA-AGE-modified caspase-3 on the induction of DNA-damage-induced apoptosis, which is associated with hepatocyte necrosis. Therefore, the suppression of necrosis, the inflammatory form of cell death, by the accumulation of GA-AGEs and GA-AGE-modified caspase-3 may represent a novel therapeutic target for the pathogenesis of NASH.</description><subject>13/2</subject><subject>13/31</subject><subject>14/1</subject><subject>14/34</subject><subject>631/80/82</subject><subject>692/4020/4021</subject><subject>Advanced glycosylation end products</subject><subject>Apoptosis</subject><subject>Camptothecin</subject><subject>Caspase</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase-3</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cell Death - physiology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>DNA Damage - drug effects</subject><subject>DNA Damage - physiology</subject><subject>Gangrene</subject><subject>Glycation End Products, Advanced - administration & dosage</subject><subject>Glycation End Products, Advanced - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakasai-Sakai, Akiko</au><au>Takata, Takanobu</au><au>Takino, Jun-ichi</au><au>Takeuchi, Masayoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of intracellular glyceraldehyde-derived advanced glycation end-products on human hepatocyte cell death</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-10-27</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>14282</spage><epage>11</epage><pages>14282-11</pages><artnum>14282</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Hepatocyte cell death is a key feature of nonalcoholic steatohepatitis (NASH); however, the pathogenesis of NASH currently remains unclear. We aimed to investigate the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (GA-AGEs) on human hepatocyte cell death. The accumulation of intracellular GA-AGEs has been associated with the induction of DNA damage and hepatocyte necrotic cell death. Among intracellular GA-AGEs, caspase-3 has been identified as a GA-AGE-modified protein with abrogated protein function. Furthermore, the activation of caspase-3 and induction of hepatocyte apoptosis by camptothecin, a DNA-damaging agent, was suppressed by a treatment with GA. These results suggest the inhibitory effects of GA-AGE-modified caspase-3 on the induction of DNA-damage-induced apoptosis, which is associated with hepatocyte necrosis. Therefore, the suppression of necrosis, the inflammatory form of cell death, by the accumulation of GA-AGEs and GA-AGE-modified caspase-3 may represent a novel therapeutic target for the pathogenesis of NASH.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29079763</pmid><doi>10.1038/s41598-017-14711-3</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/2 13/31 14/1 14/34 631/80/82 692/4020/4021 Advanced glycosylation end products Apoptosis Camptothecin Caspase Caspase 3 - metabolism Caspase-3 Cell death Cell Death - drug effects Cell Death - physiology Deoxyribonucleic acid DNA DNA damage DNA Damage - drug effects DNA Damage - physiology Gangrene Glycation End Products, Advanced - administration & dosage Glycation End Products, Advanced - metabolism Glyceraldehyde Glyceraldehyde - administration & dosage Glyceraldehyde - metabolism Glycosylation Hep G2 Cells Hepatocytes - drug effects Hepatocytes - metabolism Hepatocytes - pathology Humanities and Social Sciences Humans Inflammation Intracellular Intracellular Space - drug effects Intracellular Space - metabolism Mortality multidisciplinary Necrosis Non-alcoholic Fatty Liver Disease - drug therapy Non-alcoholic Fatty Liver Disease - metabolism Pathogenesis Protective Agents - administration & dosage Science Science (multidisciplinary) |
| title | Impact of intracellular glyceraldehyde-derived advanced glycation end-products on human hepatocyte cell death |
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