FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation
Fatty acid-binding proteins (FABPs) bind and internalize long-chain fatty acids, controlling lipid dynamics. Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this s...
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| Veröffentlicht in: | Molecular neurobiology 2019-08, Vol.56 (8), p.5763-5779 |
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| creator | Islam, Ariful Kagawa, Yoshiteru Miyazaki, Hirofumi Shil, Subrata Kumar Umaru, Banlanjo A. Yasumoto, Yuki Yamamoto, Yui Owada, Yuji |
| description | Fatty acid-binding proteins (FABPs) bind and internalize long-chain fatty acids, controlling lipid dynamics. Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase 3 were observed in FABP7 KO astrocytes under ROS stress. N-acetyl L-cysteine (NAC) application successfully rescued the ROS toxicity in FABP7 KO astrocytes. Furthermore, FABP7 overexpression in U87 human glioma cell line revealed higher LD accumulation and higher antioxidant defence enzyme (TRX, TRX reductase 1 [TRXRD1]) expression than mock transfection and protected against apoptosis signalling (p38 MAPK, SAPK/JNK and cleaved caspase 3) activation. Taken together, these data suggest that FABP7 protects astrocytes from ROS toxicity through LD formation, providing new insights linking FABP7, lipid homeostasis, and neuropsychiatric/neurodegenerative disorders, including Alzheimer’s disease and schizophrenia. |
| doi_str_mv | 10.1007/s12035-019-1489-2 |
| format | Article |
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Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase 3 were observed in FABP7 KO astrocytes under ROS stress. N-acetyl L-cysteine (NAC) application successfully rescued the ROS toxicity in FABP7 KO astrocytes. Furthermore, FABP7 overexpression in U87 human glioma cell line revealed higher LD accumulation and higher antioxidant defence enzyme (TRX, TRX reductase 1 [TRXRD1]) expression than mock transfection and protected against apoptosis signalling (p38 MAPK, SAPK/JNK and cleaved caspase 3) activation. Taken together, these data suggest that FABP7 protects astrocytes from ROS toxicity through LD formation, providing new insights linking FABP7, lipid homeostasis, and neuropsychiatric/neurodegenerative disorders, including Alzheimer’s disease and schizophrenia.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-019-1489-2</identifier><identifier>PMID: 30680690</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Accumulation ; Acetylcysteine ; Acetylcysteine - pharmacology ; Animals ; Antioxidants ; Antioxidants - metabolism ; Apoptosis ; Apoptosis - drug effects ; Astrocytes ; Astrocytes - drug effects ; Astrocytes - metabolism ; Astrocytes - pathology ; Biomedical and Life Sciences ; Biomedicine ; c-Jun protein ; Caspase ; Caspase-3 ; Cell Biology ; Cell Survival - drug effects ; Cells, Cultured ; Data processing ; Down-Regulation - drug effects ; Fatty Acid-Binding Protein 7 - metabolism ; Fatty acids ; Glioma cells ; Homeostasis ; Humans ; JNK protein ; Kinases ; Lipid Droplets - drug effects ; Lipid Droplets - metabolism ; Lipids ; MAP kinase ; Mental disorders ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria - drug effects ; Mitochondria - metabolism ; Models, Biological ; Neurobiology ; Neurodegenerative diseases ; Neurology ; Neuroprotection - drug effects ; Neurosciences ; Peroxiredoxin ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - toxicity ; Reductase ; Schizophrenia ; Signal Transduction - drug effects ; Stress ; Thioredoxin ; Toxicity ; Transcription factors ; Transfection</subject><ispartof>Molecular neurobiology, 2019-08, Vol.56 (8), p.5763-5779</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Molecular Neurobiology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-8ae6507ffc26bc043806419679ab3512c63fc299752f5e1b05f15389b2899b133</citedby><cites>FETCH-LOGICAL-c438t-8ae6507ffc26bc043806419679ab3512c63fc299752f5e1b05f15389b2899b133</cites><orcidid>0000-0002-2045-5374</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-019-1489-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-019-1489-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,41497,42566,51328</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30680690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Islam, Ariful</creatorcontrib><creatorcontrib>Kagawa, Yoshiteru</creatorcontrib><creatorcontrib>Miyazaki, Hirofumi</creatorcontrib><creatorcontrib>Shil, Subrata Kumar</creatorcontrib><creatorcontrib>Umaru, Banlanjo A.</creatorcontrib><creatorcontrib>Yasumoto, Yuki</creatorcontrib><creatorcontrib>Yamamoto, Yui</creatorcontrib><creatorcontrib>Owada, Yuji</creatorcontrib><title>FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Fatty acid-binding proteins (FABPs) bind and internalize long-chain fatty acids, controlling lipid dynamics. Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase 3 were observed in FABP7 KO astrocytes under ROS stress. N-acetyl L-cysteine (NAC) application successfully rescued the ROS toxicity in FABP7 KO astrocytes. Furthermore, FABP7 overexpression in U87 human glioma cell line revealed higher LD accumulation and higher antioxidant defence enzyme (TRX, TRX reductase 1 [TRXRD1]) expression than mock transfection and protected against apoptosis signalling (p38 MAPK, SAPK/JNK and cleaved caspase 3) activation. Taken together, these data suggest that FABP7 protects astrocytes from ROS toxicity through LD formation, providing new insights linking FABP7, lipid homeostasis, and neuropsychiatric/neurodegenerative disorders, including Alzheimer’s disease and schizophrenia.</description><subject>Accumulation</subject><subject>Acetylcysteine</subject><subject>Acetylcysteine - pharmacology</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Astrocytes</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Astrocytes - pathology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>c-Jun protein</subject><subject>Caspase</subject><subject>Caspase-3</subject><subject>Cell Biology</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Data processing</subject><subject>Down-Regulation - drug effects</subject><subject>Fatty Acid-Binding Protein 7 - metabolism</subject><subject>Fatty acids</subject><subject>Glioma cells</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>JNK protein</subject><subject>Kinases</subject><subject>Lipid Droplets - drug effects</subject><subject>Lipid Droplets - metabolism</subject><subject>Lipids</subject><subject>MAP kinase</subject><subject>Mental disorders</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Models, Biological</subject><subject>Neurobiology</subject><subject>Neurodegenerative diseases</subject><subject>Neurology</subject><subject>Neuroprotection - drug effects</subject><subject>Neurosciences</subject><subject>Peroxiredoxin</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - toxicity</subject><subject>Reductase</subject><subject>Schizophrenia</subject><subject>Signal Transduction - drug effects</subject><subject>Stress</subject><subject>Thioredoxin</subject><subject>Toxicity</subject><subject>Transcription factors</subject><subject>Transfection</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kEtPAjEUhRujEUR_gBszievR23b6WiKKj5BAFNfNzNAhQ2A6tsXIv7dkUFeu7uvcc5IPoUsMNxhA3HpMgLIUsEpxJlVKjlAfMxYnLMkx6oNUNBU8kz105v0KgBAM4hT1KHAJXEEfvYyHdzORzJwNpgw-GfrgbLkLJrbLvG58SF6nb8ncftVlHXbJZ50nk7qtF8m9s-3ahGRs3SYPtW3O0UmVr725ONQBeh8_zEdP6WT6-DwaTtIyozKkMjecgaiqkvCihLgDnmHFhcoLyjApOY0npQQjFTO4AFZhRqUqiFSqwJQO0HXn2zr7sTU-6JXduiZGaoIFCMUEh6jCnap01ntnKt26epO7ncag9_R0R09HenpPT5P4c3Vw3hYbs_j9-MEVBaQT-Hhqlsb9Rf_v-g1q83eb</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Islam, Ariful</creator><creator>Kagawa, Yoshiteru</creator><creator>Miyazaki, Hirofumi</creator><creator>Shil, Subrata Kumar</creator><creator>Umaru, Banlanjo A.</creator><creator>Yasumoto, Yuki</creator><creator>Yamamoto, Yui</creator><creator>Owada, Yuji</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>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-2045-5374</orcidid></search><sort><creationdate>20190801</creationdate><title>FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation</title><author>Islam, Ariful ; Kagawa, Yoshiteru ; Miyazaki, Hirofumi ; Shil, Subrata Kumar ; Umaru, Banlanjo A. ; Yasumoto, Yuki ; Yamamoto, Yui ; Owada, Yuji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-8ae6507ffc26bc043806419679ab3512c63fc299752f5e1b05f15389b2899b133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Accumulation</topic><topic>Acetylcysteine</topic><topic>Acetylcysteine - pharmacology</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Antioxidants - metabolism</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Astrocytes</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Astrocytes - pathology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>c-Jun protein</topic><topic>Caspase</topic><topic>Caspase-3</topic><topic>Cell Biology</topic><topic>Cell Survival - drug effects</topic><topic>Cells, Cultured</topic><topic>Data processing</topic><topic>Down-Regulation - drug effects</topic><topic>Fatty Acid-Binding Protein 7 - metabolism</topic><topic>Fatty acids</topic><topic>Glioma cells</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>JNK protein</topic><topic>Kinases</topic><topic>Lipid Droplets - drug effects</topic><topic>Lipid Droplets - metabolism</topic><topic>Lipids</topic><topic>MAP kinase</topic><topic>Mental disorders</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mitochondria - 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Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to examine the role of FABP7 in primary mouse astrocytes, focusing on its protective effect against reactive oxygen species (ROS) stress. In FABP7 knockout (KO) astrocytes, ROS induction significantly decreased LD accumulation, elevated ROS toxicity, and impaired thioredoxin (TRX) but not peroxiredoxin 1 (PRX1) signalling compared to ROS induction in wild-type astrocytes. Consequently, activation of apoptosis signalling molecules, including p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and increased expression of cleaved caspase 3 were observed in FABP7 KO astrocytes under ROS stress. N-acetyl L-cysteine (NAC) application successfully rescued the ROS toxicity in FABP7 KO astrocytes. Furthermore, FABP7 overexpression in U87 human glioma cell line revealed higher LD accumulation and higher antioxidant defence enzyme (TRX, TRX reductase 1 [TRXRD1]) expression than mock transfection and protected against apoptosis signalling (p38 MAPK, SAPK/JNK and cleaved caspase 3) activation. Taken together, these data suggest that FABP7 protects astrocytes from ROS toxicity through LD formation, providing new insights linking FABP7, lipid homeostasis, and neuropsychiatric/neurodegenerative disorders, including Alzheimer’s disease and schizophrenia.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30680690</pmid><doi>10.1007/s12035-019-1489-2</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-2045-5374</orcidid></addata></record> |
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| subjects | Accumulation Acetylcysteine Acetylcysteine - pharmacology Animals Antioxidants Antioxidants - metabolism Apoptosis Apoptosis - drug effects Astrocytes Astrocytes - drug effects Astrocytes - metabolism Astrocytes - pathology Biomedical and Life Sciences Biomedicine c-Jun protein Caspase Caspase-3 Cell Biology Cell Survival - drug effects Cells, Cultured Data processing Down-Regulation - drug effects Fatty Acid-Binding Protein 7 - metabolism Fatty acids Glioma cells Homeostasis Humans JNK protein Kinases Lipid Droplets - drug effects Lipid Droplets - metabolism Lipids MAP kinase Mental disorders Mice, Inbred C57BL Mice, Knockout Mitochondria - drug effects Mitochondria - metabolism Models, Biological Neurobiology Neurodegenerative diseases Neurology Neuroprotection - drug effects Neurosciences Peroxiredoxin Proteins Reactive oxygen species Reactive Oxygen Species - toxicity Reductase Schizophrenia Signal Transduction - drug effects Stress Thioredoxin Toxicity Transcription factors Transfection |
| title | FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation |
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