Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK- and PKC-Dependent Pathways

Curcuminoids, the predominant polyphenolic compounds in the rhizome of Curcuma longa Linn., consist of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). They exhibit multiple desirable characteristics for a neuroprotective agent including antioxidant, anti-inflammatory, and antiamy...

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Veröffentlicht in:Journal of agricultural and food chemistry 2012-01, Vol.60 (1), p.433-443
Hauptverfasser: Liao, Kuo-Kai, Wu, Ming-Jiuan, Chen, Pei-Yi, Huang, Szu-Wei, Chiu, Shu-Jun, Ho, Chi-Tang, Yen, Jui-Hung
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container_issue 1
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container_title Journal of agricultural and food chemistry
container_volume 60
creator Liao, Kuo-Kai
Wu, Ming-Jiuan
Chen, Pei-Yi
Huang, Szu-Wei
Chiu, Shu-Jun
Ho, Chi-Tang
Yen, Jui-Hung
description Curcuminoids, the predominant polyphenolic compounds in the rhizome of Curcuma longa Linn., consist of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). They exhibit multiple desirable characteristics for a neuroprotective agent including antioxidant, anti-inflammatory, and antiamyloid activities. In this work, we report the first investigation of the neurotrophic action and mechanism of curcuminoids in PC12 cells, which respond to nerve growth factor (NGF) and therefore serve as a model system for primary neuronal cells. The percentages of neurite-bearing cells for those treated with 20 μM curcumin, DMC, and BDMC for 72 h reached 21.6 ± 2.0%, 16.3 ± 2.4%, and 19.9 ± 2.5%, respectively, and were significantly higher than that of the negative control (2.0 ± 0.3%, p < 0.05). In parallel, increased expression of the neuronal differentiation markers, growth-associated protein-43 (GAP-43), and neurofilament-L (NF-L) was found in curcuminoid-treated cells. All three curcuminoids (20 μM) activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase C (PKC) signalings, and inhibition of these kinases with the respective pharmacological inhibitors effectively attenuated curcuminoid-induced neurite outgrowth. Furthermore, our results show that both curcumin and DMC, but not BDMC, induced phosphorylation of cAMP response element-binding protein (CREB) and CRE-reporter gene activity significantly (p < 0.05). These inductions were markedly attenuated by the addition of MEK/ERK or PKC inhibitor; as a consequence, ERK- and PKC-dependent pathways may be involved in curcuminoid-mediated neuritogenesis in PC12 cells. Moreover, activation of CREB coupling with CRE-dependent gene transcription may play a vital role for curcumin- or DMC-induced PC12 differentiation.
doi_str_mv 10.1021/jf203290r
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They exhibit multiple desirable characteristics for a neuroprotective agent including antioxidant, anti-inflammatory, and antiamyloid activities. In this work, we report the first investigation of the neurotrophic action and mechanism of curcuminoids in PC12 cells, which respond to nerve growth factor (NGF) and therefore serve as a model system for primary neuronal cells. The percentages of neurite-bearing cells for those treated with 20 μM curcumin, DMC, and BDMC for 72 h reached 21.6 ± 2.0%, 16.3 ± 2.4%, and 19.9 ± 2.5%, respectively, and were significantly higher than that of the negative control (2.0 ± 0.3%, p &lt; 0.05). In parallel, increased expression of the neuronal differentiation markers, growth-associated protein-43 (GAP-43), and neurofilament-L (NF-L) was found in curcuminoid-treated cells. All three curcuminoids (20 μM) activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase C (PKC) signalings, and inhibition of these kinases with the respective pharmacological inhibitors effectively attenuated curcuminoid-induced neurite outgrowth. Furthermore, our results show that both curcumin and DMC, but not BDMC, induced phosphorylation of cAMP response element-binding protein (CREB) and CRE-reporter gene activity significantly (p &lt; 0.05). These inductions were markedly attenuated by the addition of MEK/ERK or PKC inhibitor; as a consequence, ERK- and PKC-dependent pathways may be involved in curcuminoid-mediated neuritogenesis in PC12 cells. Moreover, activation of CREB coupling with CRE-dependent gene transcription may play a vital role for curcumin- or DMC-induced PC12 differentiation.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/jf203290r</identifier><identifier>PMID: 22145830</identifier><identifier>CODEN: JAFCAU</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Biological and medical sciences ; Curcuma - chemistry ; Curcuma longa ; curcumin ; Curcumin - pharmacology ; Extracellular Signal-Regulated MAP Kinases - genetics ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Food industries ; Fundamental and applied biological sciences. Psychology ; MAP Kinase Signaling System - drug effects ; mechanism of action ; mitogen-activated protein kinase ; nerve growth factor ; Neurites - drug effects ; Neurites - enzymology ; Neurites - metabolism ; Neurogenesis - drug effects ; Neurons - cytology ; Neurons - drug effects ; Neurons - enzymology ; PC12 Cells ; Plant Extracts - pharmacology ; protein kinase C ; Protein Kinase C - genetics ; Protein Kinase C - metabolism ; Rats ; transcription (genetics)</subject><ispartof>Journal of agricultural and food chemistry, 2012-01, Vol.60 (1), p.433-443</ispartof><rights>Copyright © 2011 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a434t-3483b15a596cb8be61fd8096daff9f29710679505f723d46eb68ffafe6f96b4f3</citedby><cites>FETCH-LOGICAL-a434t-3483b15a596cb8be61fd8096daff9f29710679505f723d46eb68ffafe6f96b4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jf203290r$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jf203290r$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25472465$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22145830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liao, Kuo-Kai</creatorcontrib><creatorcontrib>Wu, Ming-Jiuan</creatorcontrib><creatorcontrib>Chen, Pei-Yi</creatorcontrib><creatorcontrib>Huang, Szu-Wei</creatorcontrib><creatorcontrib>Chiu, Shu-Jun</creatorcontrib><creatorcontrib>Ho, Chi-Tang</creatorcontrib><creatorcontrib>Yen, Jui-Hung</creatorcontrib><title>Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK- and PKC-Dependent Pathways</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Curcuminoids, the predominant polyphenolic compounds in the rhizome of Curcuma longa Linn., consist of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). They exhibit multiple desirable characteristics for a neuroprotective agent including antioxidant, anti-inflammatory, and antiamyloid activities. In this work, we report the first investigation of the neurotrophic action and mechanism of curcuminoids in PC12 cells, which respond to nerve growth factor (NGF) and therefore serve as a model system for primary neuronal cells. The percentages of neurite-bearing cells for those treated with 20 μM curcumin, DMC, and BDMC for 72 h reached 21.6 ± 2.0%, 16.3 ± 2.4%, and 19.9 ± 2.5%, respectively, and were significantly higher than that of the negative control (2.0 ± 0.3%, p &lt; 0.05). In parallel, increased expression of the neuronal differentiation markers, growth-associated protein-43 (GAP-43), and neurofilament-L (NF-L) was found in curcuminoid-treated cells. All three curcuminoids (20 μM) activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase C (PKC) signalings, and inhibition of these kinases with the respective pharmacological inhibitors effectively attenuated curcuminoid-induced neurite outgrowth. Furthermore, our results show that both curcumin and DMC, but not BDMC, induced phosphorylation of cAMP response element-binding protein (CREB) and CRE-reporter gene activity significantly (p &lt; 0.05). These inductions were markedly attenuated by the addition of MEK/ERK or PKC inhibitor; as a consequence, ERK- and PKC-dependent pathways may be involved in curcuminoid-mediated neuritogenesis in PC12 cells. Moreover, activation of CREB coupling with CRE-dependent gene transcription may play a vital role for curcumin- or DMC-induced PC12 differentiation.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Curcuma - chemistry</subject><subject>Curcuma longa</subject><subject>curcumin</subject><subject>Curcumin - pharmacology</subject><subject>Extracellular Signal-Regulated MAP Kinases - genetics</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Food industries</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>mechanism of action</subject><subject>mitogen-activated protein kinase</subject><subject>nerve growth factor</subject><subject>Neurites - drug effects</subject><subject>Neurites - enzymology</subject><subject>Neurites - metabolism</subject><subject>Neurogenesis - drug effects</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - enzymology</subject><subject>PC12 Cells</subject><subject>Plant Extracts - pharmacology</subject><subject>protein kinase C</subject><subject>Protein Kinase C - genetics</subject><subject>Protein Kinase C - metabolism</subject><subject>Rats</subject><subject>transcription (genetics)</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0EFv1DAQBWALUdGlcOAPgC8IcQgdO7bjHKvQlmoLjYCeo0li72a1ibd2rKr_vka7bS-c5jCfnp4eIR8YfGPA2enGcsh5Cf4VWTDJIZOM6ddkAemZaanYMXkbwgYAtCzgDTnmnAmpc1gQrKLv4jhMbugDrb0b3WzoLxP9kO5NnFfe3c9rOky0rhinldluA53X3sXVmv48q5en57-XGcWpp_Wyyr6bnZl6M820xnl9jw_hHTmyuA3m_eGekNuL87_Vj-z65vKqOrvOUORiznKh85ZJlKXqWt0axWyvoVQ9WltaXhYMVFFKkLbgeS-UaZW2Fq1RtlStsPkJ-bLP3Xl3F02Ym3EIXaqLk3ExNCVTTGjOeZJf97LzLgRvbLPzw4j-oWHQ_Bu0eR402Y-H1NiOpn-WTwsm8PkAMHS4tR6nbggvToqCCyWT-7R3Fl2DK5_M7R8OTACw1EsVL0nYhWbjop_SXP-p9Aibl5D-</recordid><startdate>20120111</startdate><enddate>20120111</enddate><creator>Liao, Kuo-Kai</creator><creator>Wu, Ming-Jiuan</creator><creator>Chen, Pei-Yi</creator><creator>Huang, Szu-Wei</creator><creator>Chiu, Shu-Jun</creator><creator>Ho, Chi-Tang</creator><creator>Yen, Jui-Hung</creator><general>American Chemical Society</general><scope>FBQ</scope><scope>IQODW</scope><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>20120111</creationdate><title>Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK- and PKC-Dependent Pathways</title><author>Liao, Kuo-Kai ; Wu, Ming-Jiuan ; Chen, Pei-Yi ; Huang, Szu-Wei ; Chiu, Shu-Jun ; Ho, Chi-Tang ; Yen, Jui-Hung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a434t-3483b15a596cb8be61fd8096daff9f29710679505f723d46eb68ffafe6f96b4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Curcuma - chemistry</topic><topic>Curcuma longa</topic><topic>curcumin</topic><topic>Curcumin - pharmacology</topic><topic>Extracellular Signal-Regulated MAP Kinases - genetics</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Food industries</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>mechanism of action</topic><topic>mitogen-activated protein kinase</topic><topic>nerve growth factor</topic><topic>Neurites - drug effects</topic><topic>Neurites - enzymology</topic><topic>Neurites - metabolism</topic><topic>Neurogenesis - drug effects</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - enzymology</topic><topic>PC12 Cells</topic><topic>Plant Extracts - pharmacology</topic><topic>protein kinase C</topic><topic>Protein Kinase C - genetics</topic><topic>Protein Kinase C - metabolism</topic><topic>Rats</topic><topic>transcription (genetics)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liao, Kuo-Kai</creatorcontrib><creatorcontrib>Wu, Ming-Jiuan</creatorcontrib><creatorcontrib>Chen, Pei-Yi</creatorcontrib><creatorcontrib>Huang, Szu-Wei</creatorcontrib><creatorcontrib>Chiu, Shu-Jun</creatorcontrib><creatorcontrib>Ho, Chi-Tang</creatorcontrib><creatorcontrib>Yen, Jui-Hung</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><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>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liao, Kuo-Kai</au><au>Wu, Ming-Jiuan</au><au>Chen, Pei-Yi</au><au>Huang, Szu-Wei</au><au>Chiu, Shu-Jun</au><au>Ho, Chi-Tang</au><au>Yen, Jui-Hung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK- and PKC-Dependent Pathways</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2012-01-11</date><risdate>2012</risdate><volume>60</volume><issue>1</issue><spage>433</spage><epage>443</epage><pages>433-443</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><coden>JAFCAU</coden><abstract>Curcuminoids, the predominant polyphenolic compounds in the rhizome of Curcuma longa Linn., consist of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). They exhibit multiple desirable characteristics for a neuroprotective agent including antioxidant, anti-inflammatory, and antiamyloid activities. In this work, we report the first investigation of the neurotrophic action and mechanism of curcuminoids in PC12 cells, which respond to nerve growth factor (NGF) and therefore serve as a model system for primary neuronal cells. The percentages of neurite-bearing cells for those treated with 20 μM curcumin, DMC, and BDMC for 72 h reached 21.6 ± 2.0%, 16.3 ± 2.4%, and 19.9 ± 2.5%, respectively, and were significantly higher than that of the negative control (2.0 ± 0.3%, p &lt; 0.05). In parallel, increased expression of the neuronal differentiation markers, growth-associated protein-43 (GAP-43), and neurofilament-L (NF-L) was found in curcuminoid-treated cells. All three curcuminoids (20 μM) activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) and protein kinase C (PKC) signalings, and inhibition of these kinases with the respective pharmacological inhibitors effectively attenuated curcuminoid-induced neurite outgrowth. Furthermore, our results show that both curcumin and DMC, but not BDMC, induced phosphorylation of cAMP response element-binding protein (CREB) and CRE-reporter gene activity significantly (p &lt; 0.05). These inductions were markedly attenuated by the addition of MEK/ERK or PKC inhibitor; as a consequence, ERK- and PKC-dependent pathways may be involved in curcuminoid-mediated neuritogenesis in PC12 cells. Moreover, activation of CREB coupling with CRE-dependent gene transcription may play a vital role for curcumin- or DMC-induced PC12 differentiation.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>22145830</pmid><doi>10.1021/jf203290r</doi><tpages>11</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Curcuma - chemistry
Curcuma longa
curcumin
Curcumin - pharmacology
Extracellular Signal-Regulated MAP Kinases - genetics
Extracellular Signal-Regulated MAP Kinases - metabolism
Food industries
Fundamental and applied biological sciences. Psychology
MAP Kinase Signaling System - drug effects
mechanism of action
mitogen-activated protein kinase
nerve growth factor
Neurites - drug effects
Neurites - enzymology
Neurites - metabolism
Neurogenesis - drug effects
Neurons - cytology
Neurons - drug effects
Neurons - enzymology
PC12 Cells
Plant Extracts - pharmacology
protein kinase C
Protein Kinase C - genetics
Protein Kinase C - metabolism
Rats
transcription (genetics)
title Curcuminoids Promote Neurite Outgrowth in PC12 Cells through MAPK/ERK- and PKC-Dependent Pathways
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