Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling
Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the ind...
Gespeichert in:
| Veröffentlicht in: | Oxidative medicine and cellular longevity 2020, Vol.2020 (2020), p.1-18 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 18 |
|---|---|
| container_issue | 2020 |
| container_start_page | 1 |
| container_title | Oxidative medicine and cellular longevity |
| container_volume | 2020 |
| creator | Kim, Myeong Ok Rehman, Inayat U. R. Ahmad, Riaz Ahmad, Sareer Khan, Amjad Khan, Muhammad Sohail Ikram, Muhammad |
| description | Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration. |
| doi_str_mv | 10.1155/2020/5291852 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7315317</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2417984169</sourcerecordid><originalsourceid>FETCH-LOGICAL-c471t-7a2fb08ac81cb59aeed46e55e2c76588b2d9c0fddef85af19ce56f14dcdbc2d63</originalsourceid><addsrcrecordid>eNqN0cFu0zAYB3ALgdgY3DgjSxwh1HbiJL4gbYXRsqmVGJwtx_7ceEqdYieFvQgPw0PwTHhr6eDGyZb80_-z_UfoOSVvKOV8wggjE84ErTl7gI6pKFhGhCgeHvaEHKEnMV4TUuasoI_RUc5KWtG8OkY_5r51jRtc73Fv8cfFBT7tOtg6NUDE0zb03mk8u9n0Gwh2jMlln6BLpwbPo25h7RSeezPqxJffnVGD2wK-GgLEiJU3-Cwo5_E7WIGHoO4GpXS8CJZNZsuM3qHFefbr5xm-ciuvOudXT9Ejq7oIz_brCfpy_v7zdJZdLj_Mp6eXmS4qOmSVYrYhtdI11Q0XCsAUJXAOTFclr-uGGaGJNQZszZWlQgMvLS2MNo1mpsxP0Ntd7mZs1mA0-CGoTm6CW6twI3vl5L8n3rVy1W9llVOe0yoFvNwHhP7rCHGQ1_0Y0iOiTF9dibqgpUjq9U7p0McYwB4mUCJvW5S3Lcp9i4m_-PtWB_yntgRe7UDrvFHf3H_GQTJg1b1mpKgEyX8D4WKyBQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2417984169</pqid></control><display><type>article</type><title>Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>PubMed Central Open Access</source><creator>Kim, Myeong Ok ; Rehman, Inayat U. R. ; Ahmad, Riaz ; Ahmad, Sareer ; Khan, Amjad ; Khan, Muhammad Sohail ; Ikram, Muhammad</creator><contributor>Mahmoud, Ayman M. ; Ayman M Mahmoud</contributor><creatorcontrib>Kim, Myeong Ok ; Rehman, Inayat U. R. ; Ahmad, Riaz ; Ahmad, Sareer ; Khan, Amjad ; Khan, Muhammad Sohail ; Ikram, Muhammad ; Mahmoud, Ayman M. ; Ayman M Mahmoud</creatorcontrib><description>Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration.</description><identifier>ISSN: 1942-0900</identifier><identifier>EISSN: 1942-0994</identifier><identifier>DOI: 10.1155/2020/5291852</identifier><identifier>PMID: 32617137</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Aging - pathology ; Anesthesia ; Animals ; Anthracenes - pharmacology ; Antioxidants ; Apoptosis ; Apoptosis - drug effects ; Brain ; Brain Ischemia - complications ; Brain Ischemia - pathology ; Brain Ischemia - physiopathology ; Carotid arteries ; Gene expression ; Heme Oxygenase-1 - metabolism ; Hippocampus - pathology ; Ischemia ; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases - metabolism ; Kinases ; Male ; Memory Disorders - complications ; Memory Disorders - pathology ; Memory Disorders - physiopathology ; Mice, Inbred C57BL ; Models, Biological ; Neurodegenerative Diseases - complications ; Neurodegenerative Diseases - pathology ; Neurodegenerative Diseases - physiopathology ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; NF-E2-Related Factor 2 - metabolism ; NF-kappa B - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Perfusion ; Phosphorylation - drug effects ; Proteins ; Signal Transduction ; Studies ; Synapses - drug effects ; Synapses - metabolism ; Up-Regulation - drug effects ; Veins & arteries</subject><ispartof>Oxidative medicine and cellular longevity, 2020, Vol.2020 (2020), p.1-18</ispartof><rights>Copyright © 2020 Muhammad Sohail Khan et al.</rights><rights>Copyright © 2020 Muhammad Sohail Khan 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. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Muhammad Sohail Khan et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-7a2fb08ac81cb59aeed46e55e2c76588b2d9c0fddef85af19ce56f14dcdbc2d63</citedby><cites>FETCH-LOGICAL-c471t-7a2fb08ac81cb59aeed46e55e2c76588b2d9c0fddef85af19ce56f14dcdbc2d63</cites><orcidid>0000-0001-5226-4081 ; 0000-0001-7411-9483 ; 0000-0003-4317-1072</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/PMC7315317/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315317/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32617137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mahmoud, Ayman M.</contributor><contributor>Ayman M Mahmoud</contributor><creatorcontrib>Kim, Myeong Ok</creatorcontrib><creatorcontrib>Rehman, Inayat U. R.</creatorcontrib><creatorcontrib>Ahmad, Riaz</creatorcontrib><creatorcontrib>Ahmad, Sareer</creatorcontrib><creatorcontrib>Khan, Amjad</creatorcontrib><creatorcontrib>Khan, Muhammad Sohail</creatorcontrib><creatorcontrib>Ikram, Muhammad</creatorcontrib><title>Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling</title><title>Oxidative medicine and cellular longevity</title><addtitle>Oxid Med Cell Longev</addtitle><description>Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration.</description><subject>Aging - pathology</subject><subject>Anesthesia</subject><subject>Animals</subject><subject>Anthracenes - pharmacology</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Brain</subject><subject>Brain Ischemia - complications</subject><subject>Brain Ischemia - pathology</subject><subject>Brain Ischemia - physiopathology</subject><subject>Carotid arteries</subject><subject>Gene expression</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hippocampus - pathology</subject><subject>Ischemia</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Kinases</subject><subject>Male</subject><subject>Memory Disorders - complications</subject><subject>Memory Disorders - pathology</subject><subject>Memory Disorders - physiopathology</subject><subject>Mice, Inbred C57BL</subject><subject>Models, Biological</subject><subject>Neurodegenerative Diseases - complications</subject><subject>Neurodegenerative Diseases - pathology</subject><subject>Neurodegenerative Diseases - physiopathology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Perfusion</subject><subject>Phosphorylation - drug effects</subject><subject>Proteins</subject><subject>Signal Transduction</subject><subject>Studies</subject><subject>Synapses - drug effects</subject><subject>Synapses - metabolism</subject><subject>Up-Regulation - drug effects</subject><subject>Veins & arteries</subject><issn>1942-0900</issn><issn>1942-0994</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0cFu0zAYB3ALgdgY3DgjSxwh1HbiJL4gbYXRsqmVGJwtx_7ceEqdYieFvQgPw0PwTHhr6eDGyZb80_-z_UfoOSVvKOV8wggjE84ErTl7gI6pKFhGhCgeHvaEHKEnMV4TUuasoI_RUc5KWtG8OkY_5r51jRtc73Fv8cfFBT7tOtg6NUDE0zb03mk8u9n0Gwh2jMlln6BLpwbPo25h7RSeezPqxJffnVGD2wK-GgLEiJU3-Cwo5_E7WIGHoO4GpXS8CJZNZsuM3qHFefbr5xm-ciuvOudXT9Ejq7oIz_brCfpy_v7zdJZdLj_Mp6eXmS4qOmSVYrYhtdI11Q0XCsAUJXAOTFclr-uGGaGJNQZszZWlQgMvLS2MNo1mpsxP0Ntd7mZs1mA0-CGoTm6CW6twI3vl5L8n3rVy1W9llVOe0yoFvNwHhP7rCHGQ1_0Y0iOiTF9dibqgpUjq9U7p0McYwB4mUCJvW5S3Lcp9i4m_-PtWB_yntgRe7UDrvFHf3H_GQTJg1b1mpKgEyX8D4WKyBQ</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Kim, Myeong Ok</creator><creator>Rehman, Inayat U. R.</creator><creator>Ahmad, Riaz</creator><creator>Ahmad, Sareer</creator><creator>Khan, Amjad</creator><creator>Khan, Muhammad Sohail</creator><creator>Ikram, Muhammad</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5226-4081</orcidid><orcidid>https://orcid.org/0000-0001-7411-9483</orcidid><orcidid>https://orcid.org/0000-0003-4317-1072</orcidid></search><sort><creationdate>2020</creationdate><title>Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling</title><author>Kim, Myeong Ok ; Rehman, Inayat U. R. ; Ahmad, Riaz ; Ahmad, Sareer ; Khan, Amjad ; Khan, Muhammad Sohail ; Ikram, Muhammad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-7a2fb08ac81cb59aeed46e55e2c76588b2d9c0fddef85af19ce56f14dcdbc2d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aging - pathology</topic><topic>Anesthesia</topic><topic>Animals</topic><topic>Anthracenes - pharmacology</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Brain</topic><topic>Brain Ischemia - complications</topic><topic>Brain Ischemia - pathology</topic><topic>Brain Ischemia - physiopathology</topic><topic>Carotid arteries</topic><topic>Gene expression</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hippocampus - pathology</topic><topic>Ischemia</topic><topic>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Kinases</topic><topic>Male</topic><topic>Memory Disorders - complications</topic><topic>Memory Disorders - pathology</topic><topic>Memory Disorders - physiopathology</topic><topic>Mice, Inbred C57BL</topic><topic>Models, Biological</topic><topic>Neurodegenerative Diseases - complications</topic><topic>Neurodegenerative Diseases - pathology</topic><topic>Neurodegenerative Diseases - physiopathology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NF-kappa B - metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Perfusion</topic><topic>Phosphorylation - drug effects</topic><topic>Proteins</topic><topic>Signal Transduction</topic><topic>Studies</topic><topic>Synapses - drug effects</topic><topic>Synapses - metabolism</topic><topic>Up-Regulation - drug effects</topic><topic>Veins & arteries</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Myeong Ok</creatorcontrib><creatorcontrib>Rehman, Inayat U. R.</creatorcontrib><creatorcontrib>Ahmad, Riaz</creatorcontrib><creatorcontrib>Ahmad, Sareer</creatorcontrib><creatorcontrib>Khan, Amjad</creatorcontrib><creatorcontrib>Khan, Muhammad Sohail</creatorcontrib><creatorcontrib>Ikram, Muhammad</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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 Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oxidative medicine and cellular longevity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Myeong Ok</au><au>Rehman, Inayat U. R.</au><au>Ahmad, Riaz</au><au>Ahmad, Sareer</au><au>Khan, Amjad</au><au>Khan, Muhammad Sohail</au><au>Ikram, Muhammad</au><au>Mahmoud, Ayman M.</au><au>Ayman M Mahmoud</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling</atitle><jtitle>Oxidative medicine and cellular longevity</jtitle><addtitle>Oxid Med Cell Longev</addtitle><date>2020</date><risdate>2020</risdate><volume>2020</volume><issue>2020</issue><spage>1</spage><epage>18</epage><pages>1-18</pages><issn>1942-0900</issn><eissn>1942-0994</eissn><abstract>Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>32617137</pmid><doi>10.1155/2020/5291852</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0001-5226-4081</orcidid><orcidid>https://orcid.org/0000-0001-7411-9483</orcidid><orcidid>https://orcid.org/0000-0003-4317-1072</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1942-0900 |
| ispartof | Oxidative medicine and cellular longevity, 2020, Vol.2020 (2020), p.1-18 |
| issn | 1942-0900 1942-0994 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7315317 |
| source | MEDLINE; Wiley Online Library Open Access; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; PubMed Central Open Access |
| subjects | Aging - pathology Anesthesia Animals Anthracenes - pharmacology Antioxidants Apoptosis Apoptosis - drug effects Brain Brain Ischemia - complications Brain Ischemia - pathology Brain Ischemia - physiopathology Carotid arteries Gene expression Heme Oxygenase-1 - metabolism Hippocampus - pathology Ischemia JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors JNK Mitogen-Activated Protein Kinases - metabolism Kinases Male Memory Disorders - complications Memory Disorders - pathology Memory Disorders - physiopathology Mice, Inbred C57BL Models, Biological Neurodegenerative Diseases - complications Neurodegenerative Diseases - pathology Neurodegenerative Diseases - physiopathology Neurons - drug effects Neurons - metabolism Neurons - pathology NF-E2-Related Factor 2 - metabolism NF-kappa B - metabolism Oxidative stress Oxidative Stress - drug effects Perfusion Phosphorylation - drug effects Proteins Signal Transduction Studies Synapses - drug effects Synapses - metabolism Up-Regulation - drug effects Veins & arteries |
| title | Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T08%3A27%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inhibition%20of%20JNK%20Alleviates%20Chronic%20Hypoperfusion-Related%20Ischemia%20Induces%20Oxidative%20Stress%20and%20Brain%20Degeneration%20via%20Nrf2/HO-1%20and%20NF-%CE%BAB%20Signaling&rft.jtitle=Oxidative%20medicine%20and%20cellular%20longevity&rft.au=Kim,%20Myeong%20Ok&rft.date=2020&rft.volume=2020&rft.issue=2020&rft.spage=1&rft.epage=18&rft.pages=1-18&rft.issn=1942-0900&rft.eissn=1942-0994&rft_id=info:doi/10.1155/2020/5291852&rft_dat=%3Cproquest_pubme%3E2417984169%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2417984169&rft_id=info:pmid/32617137&rfr_iscdi=true |