Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway
Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agent...
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Veröffentlicht in: | Cellular and molecular neurobiology 2017-03, Vol.37 (2), p.211-222 |
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creator | Fan, Cun-dong Li, Yuan Fu, Xiao-ting Wu, Qing-jian Hou, Ya-jun Yang, Ming-feng Sun, Jing-yi Fu, Xiao-yan Zheng, Zun-cheng Sun, Bao-liang |
description | Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity. |
doi_str_mv | 10.1007/s10571-016-0362-3 |
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Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity.</description><identifier>ISSN: 0272-4340</identifier><identifier>ISSN: 1573-6830</identifier><identifier>EISSN: 1573-6830</identifier><identifier>DOI: 10.1007/s10571-016-0362-3</identifier><identifier>PMID: 26971524</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>AKT protein ; Alzheimer's disease ; Amyloid beta-Peptides - toxicity ; Animals ; Anti-Inflammatory Agents, Non-Steroidal - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Apoptosis - physiology ; Bcl protein ; Bcl-2 protein ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Cell death ; Cell Survival - drug effects ; Cell Survival - physiology ; Chemotherapy ; Curcumin ; Curcumin - pharmacology ; Cytotoxicity ; DNA damage ; Dose-Response Relationship, Drug ; Extracellular signal-regulated kinase ; MAP kinase ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Metabolic pathways ; Mitochondria ; Neurobiology ; Neurodegenerative diseases ; Neurosciences ; Neurotoxicity ; Original Research ; PC12 Cells ; Peptide Fragments - toxicity ; Pheochromocytoma cells ; Poly(ADP-ribose) polymerase ; Rats ; Reactive Oxygen Species - antagonists & inhibitors ; Reactive Oxygen Species - metabolism ; Senile plaques ; Signal Transduction - drug effects ; Signal Transduction - physiology ; β-Amyloid</subject><ispartof>Cellular and molecular neurobiology, 2017-03, Vol.37 (2), p.211-222</ispartof><rights>Springer Science+Business Media New York 2016</rights><rights>Copyright Springer Science & Business Media 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-c1f1154e19e2937c6b55c84201eeee2abe162430ea9d42ccd8d16a11838d56c93</citedby><cites>FETCH-LOGICAL-c438t-c1f1154e19e2937c6b55c84201eeee2abe162430ea9d42ccd8d16a11838d56c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10571-016-0362-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10571-016-0362-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27913,27914,41477,42546,51308</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26971524$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Cun-dong</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Fu, Xiao-ting</creatorcontrib><creatorcontrib>Wu, Qing-jian</creatorcontrib><creatorcontrib>Hou, Ya-jun</creatorcontrib><creatorcontrib>Yang, Ming-feng</creatorcontrib><creatorcontrib>Sun, Jing-yi</creatorcontrib><creatorcontrib>Fu, Xiao-yan</creatorcontrib><creatorcontrib>Zheng, Zun-cheng</creatorcontrib><creatorcontrib>Sun, Bao-liang</creatorcontrib><title>Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway</title><title>Cellular and molecular neurobiology</title><addtitle>Cell Mol Neurobiol</addtitle><addtitle>Cell Mol Neurobiol</addtitle><description>Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity.</description><subject>AKT protein</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - toxicity</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Bcl protein</subject><subject>Bcl-2 protein</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cell death</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Chemotherapy</subject><subject>Curcumin</subject><subject>Curcumin - pharmacology</subject><subject>Cytotoxicity</subject><subject>DNA damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Extracellular signal-regulated kinase</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Metabolic pathways</subject><subject>Mitochondria</subject><subject>Neurobiology</subject><subject>Neurodegenerative diseases</subject><subject>Neurosciences</subject><subject>Neurotoxicity</subject><subject>Original Research</subject><subject>PC12 Cells</subject><subject>Peptide Fragments - toxicity</subject><subject>Pheochromocytoma cells</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Rats</subject><subject>Reactive Oxygen Species - antagonists & inhibitors</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Senile plaques</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>β-Amyloid</subject><issn>0272-4340</issn><issn>1573-6830</issn><issn>1573-6830</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFuFCEYgImxsWv1AbwYEi8epPLDDDNzrJOqG1vbbPU8YeHfLc3MsAKjzgv43LLZ2hgTuXDg-z8gHyEvgJ8C59XbCLysgHFQjEslmHxEFlBWkqla8sdkwUUlWCELfkyexnjHOW84L5-QY6GaCkpRLMivFX7HEHVP_Ya-w6TZ2TD33lm2HO1k0NLPOAWf_E9nXJqpG-l1C4K22PeRrmfaTsFMgxvf0HSLdDnsfEh6THTle9w7V1c37BKt0ym7btx21L0bt1SPlp6vPtFrnW5_6PkZOdroPuLz-_2EfH1__qX9yC6uPizbswtmClknZmADUBYIDYpGVkaty9LUheCAeQm9RlCikBx1YwthjK0tKA1Qy9qWyjTyhLw-eHfBf5swpm5w0eS_6BH9FDuohVJKQKMy-uof9M5PIT9_T9W8qqSQVabgQJngYwy46XbBDTrMHfBuH6k7ROpypG4fqZN55uW9eVoPaB8m_lTJgDgAMR-NWwx_Xf1f629-qJsM</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Fan, Cun-dong</creator><creator>Li, Yuan</creator><creator>Fu, Xiao-ting</creator><creator>Wu, Qing-jian</creator><creator>Hou, Ya-jun</creator><creator>Yang, Ming-feng</creator><creator>Sun, Jing-yi</creator><creator>Fu, Xiao-yan</creator><creator>Zheng, Zun-cheng</creator><creator>Sun, Bao-liang</creator><general>Springer US</general><general>Springer Nature B.V</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>20170301</creationdate><title>Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway</title><author>Fan, Cun-dong ; Li, Yuan ; Fu, Xiao-ting ; Wu, Qing-jian ; Hou, Ya-jun ; Yang, Ming-feng ; Sun, Jing-yi ; Fu, Xiao-yan ; Zheng, Zun-cheng ; Sun, Bao-liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-c1f1154e19e2937c6b55c84201eeee2abe162430ea9d42ccd8d16a11838d56c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>AKT protein</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - toxicity</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Bcl protein</topic><topic>Bcl-2 protein</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Cell death</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>Chemotherapy</topic><topic>Curcumin</topic><topic>Curcumin - pharmacology</topic><topic>Cytotoxicity</topic><topic>DNA damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Extracellular signal-regulated kinase</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Metabolic pathways</topic><topic>Mitochondria</topic><topic>Neurobiology</topic><topic>Neurodegenerative diseases</topic><topic>Neurosciences</topic><topic>Neurotoxicity</topic><topic>Original Research</topic><topic>PC12 Cells</topic><topic>Peptide Fragments - toxicity</topic><topic>Pheochromocytoma cells</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Rats</topic><topic>Reactive Oxygen Species - antagonists & inhibitors</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Senile plaques</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>β-Amyloid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Cun-dong</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Fu, Xiao-ting</creatorcontrib><creatorcontrib>Wu, Qing-jian</creatorcontrib><creatorcontrib>Hou, Ya-jun</creatorcontrib><creatorcontrib>Yang, Ming-feng</creatorcontrib><creatorcontrib>Sun, Jing-yi</creatorcontrib><creatorcontrib>Fu, Xiao-yan</creatorcontrib><creatorcontrib>Zheng, Zun-cheng</creatorcontrib><creatorcontrib>Sun, Bao-liang</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>Cellular and molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Cun-dong</au><au>Li, Yuan</au><au>Fu, Xiao-ting</au><au>Wu, Qing-jian</au><au>Hou, Ya-jun</au><au>Yang, Ming-feng</au><au>Sun, Jing-yi</au><au>Fu, Xiao-yan</au><au>Zheng, Zun-cheng</au><au>Sun, Bao-liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway</atitle><jtitle>Cellular and molecular neurobiology</jtitle><stitle>Cell Mol Neurobiol</stitle><addtitle>Cell Mol Neurobiol</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>37</volume><issue>2</issue><spage>211</spage><epage>222</epage><pages>211-222</pages><issn>0272-4340</issn><issn>1573-6830</issn><eissn>1573-6830</eissn><abstract>Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>26971524</pmid><doi>10.1007/s10571-016-0362-3</doi><tpages>12</tpages></addata></record> |
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subjects | AKT protein Alzheimer's disease Amyloid beta-Peptides - toxicity Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Apoptosis Apoptosis - drug effects Apoptosis - physiology Bcl protein Bcl-2 protein Biomedical and Life Sciences Biomedicine Cell Biology Cell death Cell Survival - drug effects Cell Survival - physiology Chemotherapy Curcumin Curcumin - pharmacology Cytotoxicity DNA damage Dose-Response Relationship, Drug Extracellular signal-regulated kinase MAP kinase MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Metabolic pathways Mitochondria Neurobiology Neurodegenerative diseases Neurosciences Neurotoxicity Original Research PC12 Cells Peptide Fragments - toxicity Pheochromocytoma cells Poly(ADP-ribose) polymerase Rats Reactive Oxygen Species - antagonists & inhibitors Reactive Oxygen Species - metabolism Senile plaques Signal Transduction - drug effects Signal Transduction - physiology β-Amyloid |
title | Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway |
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