IGF-1 inhibits MPTP/MPP + -induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER
Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal...
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| Veröffentlicht in: | American journal of physiology: endocrinology and metabolism 2020-10, Vol.319 (4), p.E734-E743 |
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| description | Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP
) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP
-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER. |
| doi_str_mv | 10.1152/ajpendo.00071.2020 |
| format | Article |
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) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP
-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.</description><identifier>ISSN: 0193-1849</identifier><identifier>EISSN: 1522-1555</identifier><identifier>DOI: 10.1152/ajpendo.00071.2020</identifier><identifier>PMID: 32865008</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Animal models ; Animals ; Autophagy ; Autophagy - drug effects ; Dopamine ; Dopamine receptors ; Dopaminergic Neurons - drug effects ; Estrogen receptors ; Estrogens ; Growth factors ; Humans ; Hydroxylase ; Insulin ; Insulin-like growth factor I ; Insulin-Like Growth Factor I - pharmacology ; Insulin-like growth factors ; Male ; Mice ; Mice, Inbred C57BL ; Movement disorders ; MPP ; MPTP ; MPTP Poisoning - prevention & control ; MPTP Poisoning - psychology ; Neostriatum ; Neostriatum - drug effects ; Neostriatum - metabolism ; Neurodegenerative diseases ; Neurons ; Neuroprotection ; Neurotoxicity ; Oncogene Protein v-akt - metabolism ; Parkinson's disease ; Pathogenesis ; Phagocytosis ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Postural Balance - drug effects ; Pretreatment ; Proteins ; Rapamycin ; Receptor, IGF Type 1 ; Receptors, Estrogen - metabolism ; Receptors, G-Protein-Coupled - metabolism ; Signal Transduction - drug effects ; Substantia nigra ; Synuclein ; TOR protein ; TOR Serine-Threonine Kinases - metabolism ; Tyrosine</subject><ispartof>American journal of physiology: endocrinology and metabolism, 2020-10, Vol.319 (4), p.E734-E743</ispartof><rights>Copyright American Physiological Society Oct 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-3cc79e020d5befad14abcf29d742a94a8f9ba712a1ba7a21ce3f94ba27ff3eaa3</citedby><cites>FETCH-LOGICAL-c397t-3cc79e020d5befad14abcf29d742a94a8f9ba712a1ba7a21ce3f94ba27ff3eaa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32865008$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xiao-Wen</creatorcontrib><creatorcontrib>Yuan, Liang-Jie</creatorcontrib><creatorcontrib>Yang, Ye</creatorcontrib><creatorcontrib>Zhang, Mei</creatorcontrib><creatorcontrib>Chen, Wen-Fang</creatorcontrib><title>IGF-1 inhibits MPTP/MPP + -induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol Endocrinol Metab</addtitle><description>Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP
) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP
-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Animal models</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Dopamine</subject><subject>Dopamine receptors</subject><subject>Dopaminergic Neurons - drug effects</subject><subject>Estrogen receptors</subject><subject>Estrogens</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hydroxylase</subject><subject>Insulin</subject><subject>Insulin-like growth factor I</subject><subject>Insulin-Like Growth Factor I - pharmacology</subject><subject>Insulin-like growth factors</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Movement disorders</subject><subject>MPP</subject><subject>MPTP</subject><subject>MPTP Poisoning - prevention & control</subject><subject>MPTP Poisoning - psychology</subject><subject>Neostriatum</subject><subject>Neostriatum - drug effects</subject><subject>Neostriatum - metabolism</subject><subject>Neurodegenerative diseases</subject><subject>Neurons</subject><subject>Neuroprotection</subject><subject>Neurotoxicity</subject><subject>Oncogene Protein v-akt - metabolism</subject><subject>Parkinson's disease</subject><subject>Pathogenesis</subject><subject>Phagocytosis</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Postural Balance - drug effects</subject><subject>Pretreatment</subject><subject>Proteins</subject><subject>Rapamycin</subject><subject>Receptor, IGF Type 1</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Substantia nigra</subject><subject>Synuclein</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Tyrosine</subject><issn>0193-1849</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMlOwzAURS0EgjL8AAtkiSVy65HES4TaUgEiqso6eomdJoXawUlA_XvSAVZ3cYendxC6ZnTImOIjWNXWGT-klEZsyCmnR2jQG5wwpdQxGlCmBWGx1GfovGlW25yS_BSdCR7fK0rjAfqeTSeE4cqVVVa1DX5NFsnoNUnwHSaVM11uDYau9XUJyw32Dhtfw7pyNiyrHDvbBe8a3JbBd8uyV4t3g_NRMhPP5OGjJevF2xzX0JY_sMHgDJ4m4_klOings7FXB71A75Px4vGJvLxNZ48PLyQXOmqJyPNI2_4xozJbgGESsrzg2kSSg5YQFzqDiHFgvQBnuRWFlhnwqCiEBRAX6Ha_Wwf_1dmmTVe-C64_mXIpIy1jrVSf4vtUHnzTBFukdajWEDYpo-kWdXpAne5Qp1vUfenmMN1la2v-K39sxS8rRnph</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Wang, Xiao-Wen</creator><creator>Yuan, Liang-Jie</creator><creator>Yang, Ye</creator><creator>Zhang, Mei</creator><creator>Chen, Wen-Fang</creator><general>American Physiological Society</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>7QP</scope><scope>7TS</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20201001</creationdate><title>IGF-1 inhibits MPTP/MPP + -induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER</title><author>Wang, Xiao-Wen ; Yuan, Liang-Jie ; Yang, Ye ; Zhang, Mei ; Chen, Wen-Fang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-3cc79e020d5befad14abcf29d742a94a8f9ba712a1ba7a21ce3f94ba27ff3eaa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Animal models</topic><topic>Animals</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>Dopamine</topic><topic>Dopamine receptors</topic><topic>Dopaminergic Neurons - drug effects</topic><topic>Estrogen receptors</topic><topic>Estrogens</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hydroxylase</topic><topic>Insulin</topic><topic>Insulin-like growth factor I</topic><topic>Insulin-Like Growth Factor I - pharmacology</topic><topic>Insulin-like growth factors</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Movement disorders</topic><topic>MPP</topic><topic>MPTP</topic><topic>MPTP Poisoning - prevention & control</topic><topic>MPTP Poisoning - psychology</topic><topic>Neostriatum</topic><topic>Neostriatum - drug effects</topic><topic>Neostriatum - metabolism</topic><topic>Neurodegenerative diseases</topic><topic>Neurons</topic><topic>Neuroprotection</topic><topic>Neurotoxicity</topic><topic>Oncogene Protein v-akt - metabolism</topic><topic>Parkinson's disease</topic><topic>Pathogenesis</topic><topic>Phagocytosis</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Postural Balance - drug effects</topic><topic>Pretreatment</topic><topic>Proteins</topic><topic>Rapamycin</topic><topic>Receptor, IGF Type 1</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Receptors, G-Protein-Coupled - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Substantia nigra</topic><topic>Synuclein</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiao-Wen</creatorcontrib><creatorcontrib>Yuan, Liang-Jie</creatorcontrib><creatorcontrib>Yang, Ye</creatorcontrib><creatorcontrib>Zhang, Mei</creatorcontrib><creatorcontrib>Chen, Wen-Fang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>American journal of physiology: endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiao-Wen</au><au>Yuan, Liang-Jie</au><au>Yang, Ye</au><au>Zhang, Mei</au><au>Chen, Wen-Fang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IGF-1 inhibits MPTP/MPP + -induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol Endocrinol Metab</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>319</volume><issue>4</issue><spage>E734</spage><epage>E743</epage><pages>E734-E743</pages><issn>0193-1849</issn><eissn>1522-1555</eissn><abstract>Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP
) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP
-induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>32865008</pmid><doi>10.1152/ajpendo.00071.2020</doi></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Animal models Animals Autophagy Autophagy - drug effects Dopamine Dopamine receptors Dopaminergic Neurons - drug effects Estrogen receptors Estrogens Growth factors Humans Hydroxylase Insulin Insulin-like growth factor I Insulin-Like Growth Factor I - pharmacology Insulin-like growth factors Male Mice Mice, Inbred C57BL Movement disorders MPP MPTP MPTP Poisoning - prevention & control MPTP Poisoning - psychology Neostriatum Neostriatum - drug effects Neostriatum - metabolism Neurodegenerative diseases Neurons Neuroprotection Neurotoxicity Oncogene Protein v-akt - metabolism Parkinson's disease Pathogenesis Phagocytosis Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Postural Balance - drug effects Pretreatment Proteins Rapamycin Receptor, IGF Type 1 Receptors, Estrogen - metabolism Receptors, G-Protein-Coupled - metabolism Signal Transduction - drug effects Substantia nigra Synuclein TOR protein TOR Serine-Threonine Kinases - metabolism Tyrosine |
| title | IGF-1 inhibits MPTP/MPP + -induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER |
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