Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway
Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model o...
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creator | Yu, Gu-Ran Xie, Dao-Jun Chen, Huai-Zhen Jin, Shan Cui, Shen-Wei Li, Liang-Yong Tang, Lu-Lu Zhang, Jing Yang, Wen-Ming |
description | Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD. |
doi_str_mv | 10.1155/2020/3183714 |
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fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7787754</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2474855155</sourcerecordid><originalsourceid>FETCH-LOGICAL-c471t-83d177c70c81800b2d447d6d21046860e46bb6d0b430b6828ba6b248102378bf3</originalsourceid><addsrcrecordid>eNqNkU1PGzEQhi1UBJT21nNlqZdWJY2_dsdcKlUUKBKoOaSCm2WvvVmTxU7XuyH59xglTemtF9saP35n5Aehd5R8obQoxowwMuZUcqBiDx1REHQkmJSvdme4O0SvU7onhJ0CwAE65FwUpZDFEVpd6mDj0Poww1NtWtcnfBUab3yPz1eVS8kvHb7xfVw0erbGPuBpXPkql9o5_ji9-4RvonVtXofkcKzxrW9TDPi7T07nytJrPPFhTscT3c3z84num0e9foP2a90m93a7H6NfF-fTsx-j65-XV2ffrkeVANqPJLcUoAJSSSoJMcwKAba0jBJRypI4URpTWmIEJ6aUTBpdGiYkJYyDNDU_Rl83uYvBPDhbudB3ulWLzj_obq2i9urfm-AbNYtLBSABCpEDPmwDuvh7cKlX93HoQp5ZMQH5E4tsIVMnG6rqYkqdq3cdKFHPntSzJ7X1lPH3L6fawX_EZODzBmh8sPrR_2ecy4yr9V86o8Up508O7KPe</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2474855155</pqid></control><display><type>article</type><title>Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway</title><source>PubMed Central Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Wiley Online Library (Open Access Collection)</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Yu, Gu-Ran ; Xie, Dao-Jun ; Chen, Huai-Zhen ; Jin, Shan ; Cui, Shen-Wei ; Li, Liang-Yong ; Tang, Lu-Lu ; Zhang, Jing ; Yang, Wen-Ming</creator><contributor>Chen, Xiaojia ; Xiaojia Chen</contributor><creatorcontrib>Yu, Gu-Ran ; Xie, Dao-Jun ; Chen, Huai-Zhen ; Jin, Shan ; Cui, Shen-Wei ; Li, Liang-Yong ; Tang, Lu-Lu ; Zhang, Jing ; Yang, Wen-Ming ; Chen, Xiaojia ; Xiaojia Chen</creatorcontrib><description>Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2020/3183714</identifier><identifier>PMID: 33456485</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Alanine ; Alanine transaminase ; Animals ; Apoptosis ; Aspartate transaminase ; Autophagy ; Bilirubin ; Chinese medicine ; Disease ; Drug dosages ; Enzyme-linked immunosorbent assay ; Ethics ; Fluorescence microscopy ; Gene expression ; Mitochondria ; Mitophagy ; Mutation ; Neuroprotection ; Oxidative stress ; Parkin protein ; Polymerase chain reaction ; PTEN-induced putative kinase ; Reverse transcription ; Transaminase ; Transmission electron microscopy ; Western blotting ; Wilson's disease</subject><ispartof>Evidence-based complementary and alternative medicine, 2020, Vol.2020 (2020), p.1-11</ispartof><rights>Copyright © 2020 Jing Zhang et al.</rights><rights>Copyright © 2020 Jing Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Jing Zhang et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-83d177c70c81800b2d447d6d21046860e46bb6d0b430b6828ba6b248102378bf3</citedby><cites>FETCH-LOGICAL-c471t-83d177c70c81800b2d447d6d21046860e46bb6d0b430b6828ba6b248102378bf3</cites><orcidid>0000-0002-8333-8554 ; 0000-0003-4237-4855 ; 0000-0002-9356-8695 ; 0000-0001-8154-5894 ; 0000-0002-4273-6222 ; 0000-0001-8509-2140 ; 0000-0003-4102-938X ; 0000-0003-2362-1363 ; 0000-0001-8163-7318</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787754/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787754/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,4025,27925,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33456485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chen, Xiaojia</contributor><contributor>Xiaojia Chen</contributor><creatorcontrib>Yu, Gu-Ran</creatorcontrib><creatorcontrib>Xie, Dao-Jun</creatorcontrib><creatorcontrib>Chen, Huai-Zhen</creatorcontrib><creatorcontrib>Jin, Shan</creatorcontrib><creatorcontrib>Cui, Shen-Wei</creatorcontrib><creatorcontrib>Li, Liang-Yong</creatorcontrib><creatorcontrib>Tang, Lu-Lu</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Yang, Wen-Ming</creatorcontrib><title>Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.</description><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Aspartate transaminase</subject><subject>Autophagy</subject><subject>Bilirubin</subject><subject>Chinese medicine</subject><subject>Disease</subject><subject>Drug dosages</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Ethics</subject><subject>Fluorescence microscopy</subject><subject>Gene expression</subject><subject>Mitochondria</subject><subject>Mitophagy</subject><subject>Mutation</subject><subject>Neuroprotection</subject><subject>Oxidative stress</subject><subject>Parkin protein</subject><subject>Polymerase chain reaction</subject><subject>PTEN-induced putative kinase</subject><subject>Reverse transcription</subject><subject>Transaminase</subject><subject>Transmission electron microscopy</subject><subject>Western blotting</subject><subject>Wilson's 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Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway</title><author>Yu, Gu-Ran ; Xie, Dao-Jun ; Chen, Huai-Zhen ; Jin, Shan ; Cui, Shen-Wei ; Li, Liang-Yong ; Tang, Lu-Lu ; Zhang, Jing ; Yang, Wen-Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-83d177c70c81800b2d447d6d21046860e46bb6d0b430b6828ba6b248102378bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alanine</topic><topic>Alanine transaminase</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Aspartate transaminase</topic><topic>Autophagy</topic><topic>Bilirubin</topic><topic>Chinese medicine</topic><topic>Disease</topic><topic>Drug dosages</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Ethics</topic><topic>Fluorescence microscopy</topic><topic>Gene expression</topic><topic>Mitochondria</topic><topic>Mitophagy</topic><topic>Mutation</topic><topic>Neuroprotection</topic><topic>Oxidative stress</topic><topic>Parkin protein</topic><topic>Polymerase chain reaction</topic><topic>PTEN-induced putative kinase</topic><topic>Reverse transcription</topic><topic>Transaminase</topic><topic>Transmission electron microscopy</topic><topic>Western blotting</topic><topic>Wilson's disease</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Gu-Ran</creatorcontrib><creatorcontrib>Xie, Dao-Jun</creatorcontrib><creatorcontrib>Chen, Huai-Zhen</creatorcontrib><creatorcontrib>Jin, Shan</creatorcontrib><creatorcontrib>Cui, Shen-Wei</creatorcontrib><creatorcontrib>Li, Liang-Yong</creatorcontrib><creatorcontrib>Tang, Lu-Lu</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Yang, Wen-Ming</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical 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(Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Evidence-based complementary and alternative medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Gu-Ran</au><au>Xie, Dao-Jun</au><au>Chen, Huai-Zhen</au><au>Jin, Shan</au><au>Cui, Shen-Wei</au><au>Li, Liang-Yong</au><au>Tang, Lu-Lu</au><au>Zhang, Jing</au><au>Yang, Wen-Ming</au><au>Chen, Xiaojia</au><au>Xiaojia Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway</atitle><jtitle>Evidence-based complementary and alternative medicine</jtitle><addtitle>Evid Based Complement Alternat Med</addtitle><date>2020</date><risdate>2020</risdate><volume>2020</volume><issue>2020</issue><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>Objective. Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. Methods. Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. Results. Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. Conclusion. Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>33456485</pmid><doi>10.1155/2020/3183714</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8333-8554</orcidid><orcidid>https://orcid.org/0000-0003-4237-4855</orcidid><orcidid>https://orcid.org/0000-0002-9356-8695</orcidid><orcidid>https://orcid.org/0000-0001-8154-5894</orcidid><orcidid>https://orcid.org/0000-0002-4273-6222</orcidid><orcidid>https://orcid.org/0000-0001-8509-2140</orcidid><orcidid>https://orcid.org/0000-0003-4102-938X</orcidid><orcidid>https://orcid.org/0000-0003-2362-1363</orcidid><orcidid>https://orcid.org/0000-0001-8163-7318</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Alanine Alanine transaminase Animals Apoptosis Aspartate transaminase Autophagy Bilirubin Chinese medicine Disease Drug dosages Enzyme-linked immunosorbent assay Ethics Fluorescence microscopy Gene expression Mitochondria Mitophagy Mutation Neuroprotection Oxidative stress Parkin protein Polymerase chain reaction PTEN-induced putative kinase Reverse transcription Transaminase Transmission electron microscopy Western blotting Wilson's disease |
title | Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway |
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