NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition
Transcription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bov...
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| Veröffentlicht in: | Cell and tissue research 2021-09, Vol.385 (3), p.769-783 |
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| creator | Taqi, Mohamed Omar Saeed-Zidane, Mohammed Gebremedhn, Samuel Salilew-Wondim, Dessie Tholen, Ernst Neuhoff, Christiane Hoelker, Michael Schellander, Karl Tesfaye, Dawit |
| description | Transcription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bovine granulosa cells (bGCs) during exposure to OS induced by H
2
O
2
in vitro. For this, bGCs derived from ovarian follicles were cultured in vitro till their confluency and then treated with H
2
O
2
for 40 min. Twenty-four hours later, cells were subjected to various phenotypic and gene expression analyses for genes related to TFs, endoplasmic reticulum stress, apoptosis, cell proliferation, and differentiation markers. The bGCs exhibited higher reactive oxygen species accumulation, DNA fragmentation, and endoplasmic reticulum stress accompanied by reduction of mitochondrial activity after exposure to OS. In addition, higher lipid accumulation and lower cell proliferation were noticed in H
2
O
2
-challenged cells. The mRNA level of TFs including
NRF2
,
E2F1
,
KLF6
,
KLF9
,
FOS
,
SREBF1
,
SREBF2
, and
NOTCH1
was increased in H
2
O
2
-treated cells compared with non-treated controls. However, the expression level of
KLF4
and its downstream gene,
CCNB1
, were downregulated in the H
2
O
2
-challenged group. Moreover, targeted inhibition of
NRF2
using small interference RNA resulted in reduced expression of
KLF9
,
FOS
,
SREBF2
, and
NOTCH1
genes, while the expression of
KLF4
was upregulated. Taken together, bovine granulosa cells exposed to OS exhibited differential expression of various transcription factors, which are mediated by the NRF2 signaling pathway. |
| doi_str_mv | 10.1007/s00441-021-03445-4 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8526460</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A679611789</galeid><sourcerecordid>A679611789</sourcerecordid><originalsourceid>FETCH-LOGICAL-c572t-8a4df862a5f94b2b0cfa02ce773f0164a9f338e50159bad84b8678b20f3bc99c3</originalsourceid><addsrcrecordid>eNp9klFrFDEUhQdR7Fr9Az5IQBBfpt5JMpnMi1CKVaEoiIJvIZNJZlNmkzV3ZtHH_vNm3Np2RSSEwL3fPeEeTlE8r-CkAmjeIADnVQk0X8Z5XfIHxarijJYgG_mwWAEDWjZCfD8qniBeAlRciPZxccQ4gIQaVsXVpy_ntNzY3uvJ9gT9EPTow0A8Ek02GiebSLLDPOopJhIdmZIOaJLfTj4G4rTJdSQ-kC7ufLBkyP15jKiJseOIZA59log_fa8nv7MEp2QRiYmh94vE0-KR0yPaZzfvcfHt_N3Xsw_lxef3H89OL0pTN3Qqpea9k4Lq2rW8ox0Yp4Ea2zTMQSW4bh1j0tZQ1W2ne8k7KRrZUXCsM21r2HHxdq-7nbu8r7EhbzKqbfIbnX6pqL067AS_VkPcKVlTwQVkgdc3Ain-mC1OauNx2VEHG2dUtKaypVKyJqMv_0Iv45yyswslGa2kAHFHDXq0ygcX879mEVWnomlFVTWyzdTJP6h8ervx2UXrfK4fDLy6N7C2epzWGMd5MRsPQboHTYqIybpbMypQS8LUPmEqJ0z9TpjieejFfRtvR_5EKgNsD2BuhcGmu93_I3sNoZTc0w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2583218606</pqid></control><display><type>article</type><title>NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Taqi, Mohamed Omar ; Saeed-Zidane, Mohammed ; Gebremedhn, Samuel ; Salilew-Wondim, Dessie ; Tholen, Ernst ; Neuhoff, Christiane ; Hoelker, Michael ; Schellander, Karl ; Tesfaye, Dawit</creator><creatorcontrib>Taqi, Mohamed Omar ; Saeed-Zidane, Mohammed ; Gebremedhn, Samuel ; Salilew-Wondim, Dessie ; Tholen, Ernst ; Neuhoff, Christiane ; Hoelker, Michael ; Schellander, Karl ; Tesfaye, Dawit</creatorcontrib><description>Transcription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bovine granulosa cells (bGCs) during exposure to OS induced by H
2
O
2
in vitro. For this, bGCs derived from ovarian follicles were cultured in vitro till their confluency and then treated with H
2
O
2
for 40 min. Twenty-four hours later, cells were subjected to various phenotypic and gene expression analyses for genes related to TFs, endoplasmic reticulum stress, apoptosis, cell proliferation, and differentiation markers. The bGCs exhibited higher reactive oxygen species accumulation, DNA fragmentation, and endoplasmic reticulum stress accompanied by reduction of mitochondrial activity after exposure to OS. In addition, higher lipid accumulation and lower cell proliferation were noticed in H
2
O
2
-challenged cells. The mRNA level of TFs including
NRF2
,
E2F1
,
KLF6
,
KLF9
,
FOS
,
SREBF1
,
SREBF2
, and
NOTCH1
was increased in H
2
O
2
-treated cells compared with non-treated controls. However, the expression level of
KLF4
and its downstream gene,
CCNB1
, were downregulated in the H
2
O
2
-challenged group. Moreover, targeted inhibition of
NRF2
using small interference RNA resulted in reduced expression of
KLF9
,
FOS
,
SREBF2
, and
NOTCH1
genes, while the expression of
KLF4
was upregulated. Taken together, bovine granulosa cells exposed to OS exhibited differential expression of various transcription factors, which are mediated by the NRF2 signaling pathway.</description><identifier>ISSN: 0302-766X</identifier><identifier>EISSN: 1432-0878</identifier><identifier>DOI: 10.1007/s00441-021-03445-4</identifier><identifier>PMID: 34008050</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Cattle ; Cell differentiation ; Cell growth ; Cell proliferation ; DNA binding proteins ; DNA fragmentation ; Endoplasmic reticulum ; Ethylenediaminetetraacetic acid ; Female ; Follicles ; Folliculogenesis ; Gene expression ; Genes ; Granulosa cells ; Granulosa Cells - metabolism ; Human Genetics ; Hydrogen peroxide ; KLF4 protein ; Mitochondria ; Molecular Medicine ; NF-E2-Related Factor 2 - metabolism ; Notch1 protein ; NRF2 protein ; Oxidative stress ; Oxidative Stress - drug effects ; Proteomics ; Reactive oxygen species ; Regular ; Regular Article ; RNA ; RNA-mediated interference ; Signal Transduction ; siRNA ; Transcription factors ; Transcription Factors - metabolism ; Transfection</subject><ispartof>Cell and tissue research, 2021-09, Vol.385 (3), p.769-783</ispartof><rights>This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021</rights><rights>2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.</rights><rights>COPYRIGHT 2021 Springer</rights><rights>This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c572t-8a4df862a5f94b2b0cfa02ce773f0164a9f338e50159bad84b8678b20f3bc99c3</citedby><cites>FETCH-LOGICAL-c572t-8a4df862a5f94b2b0cfa02ce773f0164a9f338e50159bad84b8678b20f3bc99c3</cites><orcidid>0000-0001-8166-0606</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/s00441-021-03445-4$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00441-021-03445-4$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34008050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taqi, Mohamed Omar</creatorcontrib><creatorcontrib>Saeed-Zidane, Mohammed</creatorcontrib><creatorcontrib>Gebremedhn, Samuel</creatorcontrib><creatorcontrib>Salilew-Wondim, Dessie</creatorcontrib><creatorcontrib>Tholen, Ernst</creatorcontrib><creatorcontrib>Neuhoff, Christiane</creatorcontrib><creatorcontrib>Hoelker, Michael</creatorcontrib><creatorcontrib>Schellander, Karl</creatorcontrib><creatorcontrib>Tesfaye, Dawit</creatorcontrib><title>NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition</title><title>Cell and tissue research</title><addtitle>Cell Tissue Res</addtitle><addtitle>Cell Tissue Res</addtitle><description>Transcription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bovine granulosa cells (bGCs) during exposure to OS induced by H
2
O
2
in vitro. For this, bGCs derived from ovarian follicles were cultured in vitro till their confluency and then treated with H
2
O
2
for 40 min. Twenty-four hours later, cells were subjected to various phenotypic and gene expression analyses for genes related to TFs, endoplasmic reticulum stress, apoptosis, cell proliferation, and differentiation markers. The bGCs exhibited higher reactive oxygen species accumulation, DNA fragmentation, and endoplasmic reticulum stress accompanied by reduction of mitochondrial activity after exposure to OS. In addition, higher lipid accumulation and lower cell proliferation were noticed in H
2
O
2
-challenged cells. The mRNA level of TFs including
NRF2
,
E2F1
,
KLF6
,
KLF9
,
FOS
,
SREBF1
,
SREBF2
, and
NOTCH1
was increased in H
2
O
2
-treated cells compared with non-treated controls. However, the expression level of
KLF4
and its downstream gene,
CCNB1
, were downregulated in the H
2
O
2
-challenged group. Moreover, targeted inhibition of
NRF2
using small interference RNA resulted in reduced expression of
KLF9
,
FOS
,
SREBF2
, and
NOTCH1
genes, while the expression of
KLF4
was upregulated. Taken together, bovine granulosa cells exposed to OS exhibited differential expression of various transcription factors, which are mediated by the NRF2 signaling pathway.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cattle</subject><subject>Cell differentiation</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>DNA binding proteins</subject><subject>DNA fragmentation</subject><subject>Endoplasmic reticulum</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Female</subject><subject>Follicles</subject><subject>Folliculogenesis</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Granulosa cells</subject><subject>Granulosa Cells - metabolism</subject><subject>Human Genetics</subject><subject>Hydrogen peroxide</subject><subject>KLF4 protein</subject><subject>Mitochondria</subject><subject>Molecular Medicine</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Notch1 protein</subject><subject>NRF2 protein</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Proteomics</subject><subject>Reactive oxygen species</subject><subject>Regular</subject><subject>Regular Article</subject><subject>RNA</subject><subject>RNA-mediated interference</subject><subject>Signal Transduction</subject><subject>siRNA</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Transfection</subject><issn>0302-766X</issn><issn>1432-0878</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp9klFrFDEUhQdR7Fr9Az5IQBBfpt5JMpnMi1CKVaEoiIJvIZNJZlNmkzV3ZtHH_vNm3Np2RSSEwL3fPeEeTlE8r-CkAmjeIADnVQk0X8Z5XfIHxarijJYgG_mwWAEDWjZCfD8qniBeAlRciPZxccQ4gIQaVsXVpy_ntNzY3uvJ9gT9EPTow0A8Ek02GiebSLLDPOopJhIdmZIOaJLfTj4G4rTJdSQ-kC7ufLBkyP15jKiJseOIZA59log_fa8nv7MEp2QRiYmh94vE0-KR0yPaZzfvcfHt_N3Xsw_lxef3H89OL0pTN3Qqpea9k4Lq2rW8ox0Yp4Ea2zTMQSW4bh1j0tZQ1W2ne8k7KRrZUXCsM21r2HHxdq-7nbu8r7EhbzKqbfIbnX6pqL067AS_VkPcKVlTwQVkgdc3Ain-mC1OauNx2VEHG2dUtKaypVKyJqMv_0Iv45yyswslGa2kAHFHDXq0ygcX879mEVWnomlFVTWyzdTJP6h8ervx2UXrfK4fDLy6N7C2epzWGMd5MRsPQboHTYqIybpbMypQS8LUPmEqJ0z9TpjieejFfRtvR_5EKgNsD2BuhcGmu93_I3sNoZTc0w</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Taqi, Mohamed Omar</creator><creator>Saeed-Zidane, Mohammed</creator><creator>Gebremedhn, Samuel</creator><creator>Salilew-Wondim, Dessie</creator><creator>Tholen, Ernst</creator><creator>Neuhoff, Christiane</creator><creator>Hoelker, Michael</creator><creator>Schellander, Karl</creator><creator>Tesfaye, Dawit</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>C6C</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>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SS</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</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>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8166-0606</orcidid></search><sort><creationdate>20210901</creationdate><title>NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition</title><author>Taqi, Mohamed Omar ; Saeed-Zidane, Mohammed ; Gebremedhn, Samuel ; Salilew-Wondim, Dessie ; Tholen, Ernst ; Neuhoff, Christiane ; Hoelker, Michael ; Schellander, Karl ; Tesfaye, Dawit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-8a4df862a5f94b2b0cfa02ce773f0164a9f338e50159bad84b8678b20f3bc99c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cattle</topic><topic>Cell differentiation</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>DNA binding proteins</topic><topic>DNA fragmentation</topic><topic>Endoplasmic reticulum</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Female</topic><topic>Follicles</topic><topic>Folliculogenesis</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Granulosa cells</topic><topic>Granulosa Cells - metabolism</topic><topic>Human Genetics</topic><topic>Hydrogen peroxide</topic><topic>KLF4 protein</topic><topic>Mitochondria</topic><topic>Molecular Medicine</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Notch1 protein</topic><topic>NRF2 protein</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Proteomics</topic><topic>Reactive oxygen species</topic><topic>Regular</topic><topic>Regular Article</topic><topic>RNA</topic><topic>RNA-mediated interference</topic><topic>Signal Transduction</topic><topic>siRNA</topic><topic>Transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taqi, Mohamed Omar</creatorcontrib><creatorcontrib>Saeed-Zidane, Mohammed</creatorcontrib><creatorcontrib>Gebremedhn, Samuel</creatorcontrib><creatorcontrib>Salilew-Wondim, Dessie</creatorcontrib><creatorcontrib>Tholen, Ernst</creatorcontrib><creatorcontrib>Neuhoff, Christiane</creatorcontrib><creatorcontrib>Hoelker, Michael</creatorcontrib><creatorcontrib>Schellander, Karl</creatorcontrib><creatorcontrib>Tesfaye, Dawit</creatorcontrib><collection>Springer Nature OA Free Journals</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell and tissue research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taqi, Mohamed Omar</au><au>Saeed-Zidane, Mohammed</au><au>Gebremedhn, Samuel</au><au>Salilew-Wondim, Dessie</au><au>Tholen, Ernst</au><au>Neuhoff, Christiane</au><au>Hoelker, Michael</au><au>Schellander, Karl</au><au>Tesfaye, Dawit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition</atitle><jtitle>Cell and tissue research</jtitle><stitle>Cell Tissue Res</stitle><addtitle>Cell Tissue Res</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>385</volume><issue>3</issue><spage>769</spage><epage>783</epage><pages>769-783</pages><issn>0302-766X</issn><eissn>1432-0878</eissn><abstract>Transcription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bovine granulosa cells (bGCs) during exposure to OS induced by H
2
O
2
in vitro. For this, bGCs derived from ovarian follicles were cultured in vitro till their confluency and then treated with H
2
O
2
for 40 min. Twenty-four hours later, cells were subjected to various phenotypic and gene expression analyses for genes related to TFs, endoplasmic reticulum stress, apoptosis, cell proliferation, and differentiation markers. The bGCs exhibited higher reactive oxygen species accumulation, DNA fragmentation, and endoplasmic reticulum stress accompanied by reduction of mitochondrial activity after exposure to OS. In addition, higher lipid accumulation and lower cell proliferation were noticed in H
2
O
2
-challenged cells. The mRNA level of TFs including
NRF2
,
E2F1
,
KLF6
,
KLF9
,
FOS
,
SREBF1
,
SREBF2
, and
NOTCH1
was increased in H
2
O
2
-treated cells compared with non-treated controls. However, the expression level of
KLF4
and its downstream gene,
CCNB1
, were downregulated in the H
2
O
2
-challenged group. Moreover, targeted inhibition of
NRF2
using small interference RNA resulted in reduced expression of
KLF9
,
FOS
,
SREBF2
, and
NOTCH1
genes, while the expression of
KLF4
was upregulated. Taken together, bovine granulosa cells exposed to OS exhibited differential expression of various transcription factors, which are mediated by the NRF2 signaling pathway.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>34008050</pmid><doi>10.1007/s00441-021-03445-4</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-8166-0606</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0302-766X |
| ispartof | Cell and tissue research, 2021-09, Vol.385 (3), p.769-783 |
| issn | 0302-766X 1432-0878 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8526460 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Apoptosis Biomedical and Life Sciences Biomedicine Cattle Cell differentiation Cell growth Cell proliferation DNA binding proteins DNA fragmentation Endoplasmic reticulum Ethylenediaminetetraacetic acid Female Follicles Folliculogenesis Gene expression Genes Granulosa cells Granulosa Cells - metabolism Human Genetics Hydrogen peroxide KLF4 protein Mitochondria Molecular Medicine NF-E2-Related Factor 2 - metabolism Notch1 protein NRF2 protein Oxidative stress Oxidative Stress - drug effects Proteomics Reactive oxygen species Regular Regular Article RNA RNA-mediated interference Signal Transduction siRNA Transcription factors Transcription Factors - metabolism Transfection |
| title | NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition |
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