Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation
Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intesti...
Gespeichert in:
| Veröffentlicht in: | Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2021-05, Vol.85, p.111087, Article 111087 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | |
| container_start_page | 111087 |
| container_title | Nutrition (Burbank, Los Angeles County, Calif.) |
| container_volume | 85 |
| creator | de Freitas, Rosa Elayne Marques Medeiros, Pedro Henrique Quintela Soares Rodrigues, Francisco Adelvane de Paulo Clementino, Marco Antonio de Freitas Fernandes, Camila da Silva, Antonio Vinicios Alves Prata, Mara de Moura Gondim Cavalcante, Paloma Araújo Lima, Aldo Ângelo Moreira Havt, Alexandre |
| description | Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6).
IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 μM. Proliferation, apoptosis/necrosis, cell cycle process, and gene transcription were assessed.
Nutrient deprivation for 6, 12, 24, or 48 h decreased cell proliferation, and retinyl palmitate further decreased it after 24 and 48 h. Apoptosis rates were reduced by undernourishment and further reduced by retinyl palmitate after 48 h; whereas necrosis rates were unaltered. Undernourishment induced overall cell quiescence, increased percentage of cells in G0/G1 phase and decreased percentage of cells in S phase after 12 h and in G2/M phases at 6, 12, and 24 h after treatment. Both retinoids also showed cell quiescence induction with less cells in G2/M phases after 48 h, whereas only retinol showed significant modulation of G0/G1 and S phases. Both retinoids also increased markers of cell differentiation Fabp and Iap gene transcriptions in about fivefold rates after 42 h. Furthermore, specific gene transcriptions related to MAP kinase signaling pathway regulation of cell differentiation and cell cycle regulation were triggered by retinoids in undernourished IEC-6, with higher levels of expression for Atf2 and C-jun genes.
These findings indicated that both vitamin A derivatives induce further survival mechanisms in undernourished intestinal epithelial crypt cells. These mechanisms include increased cell quiescence, decreased apoptosis, increased cell differentiation, and transcription of genes related to MAP kinase signaling pathway.
•Proliferation and apoptosis are impaired by retinyl palmitate in undernourished intestinal epithelial cells.•Vitamin A derivatives induce further survival and differentiation of undernourished intestinal epithelial cells.•MAP kinase signaling pathway via JNK is triggered by vitamin A derivatives in undernourished intestinal epithelial cells. |
| doi_str_mv | 10.1016/j.nut.2020.111087 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2510227954</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0899900720303701</els_id><sourcerecordid>2510227954</sourcerecordid><originalsourceid>FETCH-LOGICAL-c333t-5449189e4bc7c6f3e08bef7ba2bd38bfa310a301f3b964336dbddfe85c4038c73</originalsourceid><addsrcrecordid>eNp9kEtPAyEUhYnRaK3-ADeGxPVUGJgHcWWMr8TExOiaMHBRmulQgRq79J_L2OrSFdxwz-GcD6ETSmaU0Pp8PhtWaVaSMs-UkrbZQRPaNqygJee7aEJaIQpBSHOADmOcE0KoqMU-OmCs4lXF2QR9PUFyg3cmYgO9WmMNfY_1WveAl8G_BojR-QGrwYzzwifAxlkLAYbkVBrfvMVuSBCzkeoxLF16g97l6-gVMXwufQSDk8c5bnBZmP9aBvfxIz9Ce1b1EY635xS93Fw_X90VD4-391eXD4VmjKWi4lzQVgDvdKNry4C0HdimU2VnWNtZxShRjFDLOlFzxmrTGWOhrTQnrNUNm6KzjW-u8b7KaeXcr0JOHGVZUVKWjchEpohutnTwMQawMgddqLCWlMgRupzL3EKO0OUGetacbp1X3QLMn-KXcl642CxA7vfhIMioMwYNxgXQSRrv_rH_Bq7sldc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2510227954</pqid></control><display><type>article</type><title>Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation</title><source>Elsevier ScienceDirect Journals</source><creator>de Freitas, Rosa Elayne Marques ; Medeiros, Pedro Henrique Quintela Soares ; Rodrigues, Francisco Adelvane de Paulo ; Clementino, Marco Antonio de Freitas ; Fernandes, Camila ; da Silva, Antonio Vinicios Alves ; Prata, Mara de Moura Gondim ; Cavalcante, Paloma Araújo ; Lima, Aldo Ângelo Moreira ; Havt, Alexandre</creator><creatorcontrib>de Freitas, Rosa Elayne Marques ; Medeiros, Pedro Henrique Quintela Soares ; Rodrigues, Francisco Adelvane de Paulo ; Clementino, Marco Antonio de Freitas ; Fernandes, Camila ; da Silva, Antonio Vinicios Alves ; Prata, Mara de Moura Gondim ; Cavalcante, Paloma Araújo ; Lima, Aldo Ângelo Moreira ; Havt, Alexandre</creatorcontrib><description>Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6).
IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 μM. Proliferation, apoptosis/necrosis, cell cycle process, and gene transcription were assessed.
Nutrient deprivation for 6, 12, 24, or 48 h decreased cell proliferation, and retinyl palmitate further decreased it after 24 and 48 h. Apoptosis rates were reduced by undernourishment and further reduced by retinyl palmitate after 48 h; whereas necrosis rates were unaltered. Undernourishment induced overall cell quiescence, increased percentage of cells in G0/G1 phase and decreased percentage of cells in S phase after 12 h and in G2/M phases at 6, 12, and 24 h after treatment. Both retinoids also showed cell quiescence induction with less cells in G2/M phases after 48 h, whereas only retinol showed significant modulation of G0/G1 and S phases. Both retinoids also increased markers of cell differentiation Fabp and Iap gene transcriptions in about fivefold rates after 42 h. Furthermore, specific gene transcriptions related to MAP kinase signaling pathway regulation of cell differentiation and cell cycle regulation were triggered by retinoids in undernourished IEC-6, with higher levels of expression for Atf2 and C-jun genes.
These findings indicated that both vitamin A derivatives induce further survival mechanisms in undernourished intestinal epithelial crypt cells. These mechanisms include increased cell quiescence, decreased apoptosis, increased cell differentiation, and transcription of genes related to MAP kinase signaling pathway.
•Proliferation and apoptosis are impaired by retinyl palmitate in undernourished intestinal epithelial cells.•Vitamin A derivatives induce further survival and differentiation of undernourished intestinal epithelial cells.•MAP kinase signaling pathway via JNK is triggered by vitamin A derivatives in undernourished intestinal epithelial cells.</description><identifier>ISSN: 0899-9007</identifier><identifier>EISSN: 1873-1244</identifier><identifier>DOI: 10.1016/j.nut.2020.111087</identifier><identifier>PMID: 33545543</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Apoptosis ; c-Jun protein ; Cell cycle ; Cell differentiation ; Cell growth ; Cell proliferation ; Children & youth ; Crypts ; Deprivation ; Developing countries ; Diarrhea ; Differentiation (biology) ; Epithelial cells ; Epithelium ; Fatty acid-binding protein ; Flow cytometry ; G1 phase ; Gene expression ; Genes ; Glutamine ; Intestinal epithelium ; Intestine ; Kinases ; LDCs ; Malnutrition ; MAP kinase ; Modulation ; Necrosis ; Nutrient deficiency ; Nutrients ; Palmitic acid ; Phases ; Proteins ; Public health ; Retinene ; Retinoids ; S phase ; Signal transduction ; Signaling ; Software ; Transcription factors ; Undernutrition ; Vitamin A</subject><ispartof>Nutrition (Burbank, Los Angeles County, Calif.), 2021-05, Vol.85, p.111087, Article 111087</ispartof><rights>2020 Elsevier Inc.</rights><rights>Copyright © 2020 Elsevier Inc. All rights reserved.</rights><rights>2020. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c333t-5449189e4bc7c6f3e08bef7ba2bd38bfa310a301f3b964336dbddfe85c4038c73</cites><orcidid>0000-0002-0628-8047 ; 0000-0002-4546-2976</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0899900720303701$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33545543$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Freitas, Rosa Elayne Marques</creatorcontrib><creatorcontrib>Medeiros, Pedro Henrique Quintela Soares</creatorcontrib><creatorcontrib>Rodrigues, Francisco Adelvane de Paulo</creatorcontrib><creatorcontrib>Clementino, Marco Antonio de Freitas</creatorcontrib><creatorcontrib>Fernandes, Camila</creatorcontrib><creatorcontrib>da Silva, Antonio Vinicios Alves</creatorcontrib><creatorcontrib>Prata, Mara de Moura Gondim</creatorcontrib><creatorcontrib>Cavalcante, Paloma Araújo</creatorcontrib><creatorcontrib>Lima, Aldo Ângelo Moreira</creatorcontrib><creatorcontrib>Havt, Alexandre</creatorcontrib><title>Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation</title><title>Nutrition (Burbank, Los Angeles County, Calif.)</title><addtitle>Nutrition</addtitle><description>Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6).
IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 μM. Proliferation, apoptosis/necrosis, cell cycle process, and gene transcription were assessed.
Nutrient deprivation for 6, 12, 24, or 48 h decreased cell proliferation, and retinyl palmitate further decreased it after 24 and 48 h. Apoptosis rates were reduced by undernourishment and further reduced by retinyl palmitate after 48 h; whereas necrosis rates were unaltered. Undernourishment induced overall cell quiescence, increased percentage of cells in G0/G1 phase and decreased percentage of cells in S phase after 12 h and in G2/M phases at 6, 12, and 24 h after treatment. Both retinoids also showed cell quiescence induction with less cells in G2/M phases after 48 h, whereas only retinol showed significant modulation of G0/G1 and S phases. Both retinoids also increased markers of cell differentiation Fabp and Iap gene transcriptions in about fivefold rates after 42 h. Furthermore, specific gene transcriptions related to MAP kinase signaling pathway regulation of cell differentiation and cell cycle regulation were triggered by retinoids in undernourished IEC-6, with higher levels of expression for Atf2 and C-jun genes.
These findings indicated that both vitamin A derivatives induce further survival mechanisms in undernourished intestinal epithelial crypt cells. These mechanisms include increased cell quiescence, decreased apoptosis, increased cell differentiation, and transcription of genes related to MAP kinase signaling pathway.
•Proliferation and apoptosis are impaired by retinyl palmitate in undernourished intestinal epithelial cells.•Vitamin A derivatives induce further survival and differentiation of undernourished intestinal epithelial cells.•MAP kinase signaling pathway via JNK is triggered by vitamin A derivatives in undernourished intestinal epithelial cells.</description><subject>Apoptosis</subject><subject>c-Jun protein</subject><subject>Cell cycle</subject><subject>Cell differentiation</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Children & youth</subject><subject>Crypts</subject><subject>Deprivation</subject><subject>Developing countries</subject><subject>Diarrhea</subject><subject>Differentiation (biology)</subject><subject>Epithelial cells</subject><subject>Epithelium</subject><subject>Fatty acid-binding protein</subject><subject>Flow cytometry</subject><subject>G1 phase</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Glutamine</subject><subject>Intestinal epithelium</subject><subject>Intestine</subject><subject>Kinases</subject><subject>LDCs</subject><subject>Malnutrition</subject><subject>MAP kinase</subject><subject>Modulation</subject><subject>Necrosis</subject><subject>Nutrient deficiency</subject><subject>Nutrients</subject><subject>Palmitic acid</subject><subject>Phases</subject><subject>Proteins</subject><subject>Public health</subject><subject>Retinene</subject><subject>Retinoids</subject><subject>S phase</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Software</subject><subject>Transcription factors</subject><subject>Undernutrition</subject><subject>Vitamin A</subject><issn>0899-9007</issn><issn>1873-1244</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kEtPAyEUhYnRaK3-ADeGxPVUGJgHcWWMr8TExOiaMHBRmulQgRq79J_L2OrSFdxwz-GcD6ETSmaU0Pp8PhtWaVaSMs-UkrbZQRPaNqygJee7aEJaIQpBSHOADmOcE0KoqMU-OmCs4lXF2QR9PUFyg3cmYgO9WmMNfY_1WveAl8G_BojR-QGrwYzzwifAxlkLAYbkVBrfvMVuSBCzkeoxLF16g97l6-gVMXwufQSDk8c5bnBZmP9aBvfxIz9Ce1b1EY635xS93Fw_X90VD4-391eXD4VmjKWi4lzQVgDvdKNry4C0HdimU2VnWNtZxShRjFDLOlFzxmrTGWOhrTQnrNUNm6KzjW-u8b7KaeXcr0JOHGVZUVKWjchEpohutnTwMQawMgddqLCWlMgRupzL3EKO0OUGetacbp1X3QLMn-KXcl642CxA7vfhIMioMwYNxgXQSRrv_rH_Bq7sldc</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>de Freitas, Rosa Elayne Marques</creator><creator>Medeiros, Pedro Henrique Quintela Soares</creator><creator>Rodrigues, Francisco Adelvane de Paulo</creator><creator>Clementino, Marco Antonio de Freitas</creator><creator>Fernandes, Camila</creator><creator>da Silva, Antonio Vinicios Alves</creator><creator>Prata, Mara de Moura Gondim</creator><creator>Cavalcante, Paloma Araújo</creator><creator>Lima, Aldo Ângelo Moreira</creator><creator>Havt, Alexandre</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RQ</scope><scope>7RV</scope><scope>7TS</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-0628-8047</orcidid><orcidid>https://orcid.org/0000-0002-4546-2976</orcidid></search><sort><creationdate>202105</creationdate><title>Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation</title><author>de Freitas, Rosa Elayne Marques ; Medeiros, Pedro Henrique Quintela Soares ; Rodrigues, Francisco Adelvane de Paulo ; Clementino, Marco Antonio de Freitas ; Fernandes, Camila ; da Silva, Antonio Vinicios Alves ; Prata, Mara de Moura Gondim ; Cavalcante, Paloma Araújo ; Lima, Aldo Ângelo Moreira ; Havt, Alexandre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c333t-5449189e4bc7c6f3e08bef7ba2bd38bfa310a301f3b964336dbddfe85c4038c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Apoptosis</topic><topic>c-Jun protein</topic><topic>Cell cycle</topic><topic>Cell differentiation</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Children & youth</topic><topic>Crypts</topic><topic>Deprivation</topic><topic>Developing countries</topic><topic>Diarrhea</topic><topic>Differentiation (biology)</topic><topic>Epithelial cells</topic><topic>Epithelium</topic><topic>Fatty acid-binding protein</topic><topic>Flow cytometry</topic><topic>G1 phase</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Glutamine</topic><topic>Intestinal epithelium</topic><topic>Intestine</topic><topic>Kinases</topic><topic>LDCs</topic><topic>Malnutrition</topic><topic>MAP kinase</topic><topic>Modulation</topic><topic>Necrosis</topic><topic>Nutrient deficiency</topic><topic>Nutrients</topic><topic>Palmitic acid</topic><topic>Phases</topic><topic>Proteins</topic><topic>Public health</topic><topic>Retinene</topic><topic>Retinoids</topic><topic>S phase</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Software</topic><topic>Transcription factors</topic><topic>Undernutrition</topic><topic>Vitamin A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Freitas, Rosa Elayne Marques</creatorcontrib><creatorcontrib>Medeiros, Pedro Henrique Quintela Soares</creatorcontrib><creatorcontrib>Rodrigues, Francisco Adelvane de Paulo</creatorcontrib><creatorcontrib>Clementino, Marco Antonio de Freitas</creatorcontrib><creatorcontrib>Fernandes, Camila</creatorcontrib><creatorcontrib>da Silva, Antonio Vinicios Alves</creatorcontrib><creatorcontrib>Prata, Mara de Moura Gondim</creatorcontrib><creatorcontrib>Cavalcante, Paloma Araújo</creatorcontrib><creatorcontrib>Lima, Aldo Ângelo Moreira</creatorcontrib><creatorcontrib>Havt, Alexandre</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Career & Technical Education Database</collection><collection>Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health 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>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</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>SciTech Premium Collection</collection><collection>British Nursing Index</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>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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 Basic</collection><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Freitas, Rosa Elayne Marques</au><au>Medeiros, Pedro Henrique Quintela Soares</au><au>Rodrigues, Francisco Adelvane de Paulo</au><au>Clementino, Marco Antonio de Freitas</au><au>Fernandes, Camila</au><au>da Silva, Antonio Vinicios Alves</au><au>Prata, Mara de Moura Gondim</au><au>Cavalcante, Paloma Araújo</au><au>Lima, Aldo Ângelo Moreira</au><au>Havt, Alexandre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation</atitle><jtitle>Nutrition (Burbank, Los Angeles County, Calif.)</jtitle><addtitle>Nutrition</addtitle><date>2021-05</date><risdate>2021</risdate><volume>85</volume><spage>111087</spage><pages>111087-</pages><artnum>111087</artnum><issn>0899-9007</issn><eissn>1873-1244</eissn><abstract>Vitamin A is commonly recommended as a treatment for diarrhea and undernutrition; however, little is known about the underlying cellular mechanisms. The aim of this study was to investigate the modulation of cell cycle by vitamin A derivatives (retinyl palmitate or retinol) in undernourished intestinal epithelial crypts (IEC-6).
IEC-6 cells were exposed to nutrient deprivation (no serum and no glutamine) and supplemented with retinyl palmitate or retinol at a range of 2 to 20 μM. Proliferation, apoptosis/necrosis, cell cycle process, and gene transcription were assessed.
Nutrient deprivation for 6, 12, 24, or 48 h decreased cell proliferation, and retinyl palmitate further decreased it after 24 and 48 h. Apoptosis rates were reduced by undernourishment and further reduced by retinyl palmitate after 48 h; whereas necrosis rates were unaltered. Undernourishment induced overall cell quiescence, increased percentage of cells in G0/G1 phase and decreased percentage of cells in S phase after 12 h and in G2/M phases at 6, 12, and 24 h after treatment. Both retinoids also showed cell quiescence induction with less cells in G2/M phases after 48 h, whereas only retinol showed significant modulation of G0/G1 and S phases. Both retinoids also increased markers of cell differentiation Fabp and Iap gene transcriptions in about fivefold rates after 42 h. Furthermore, specific gene transcriptions related to MAP kinase signaling pathway regulation of cell differentiation and cell cycle regulation were triggered by retinoids in undernourished IEC-6, with higher levels of expression for Atf2 and C-jun genes.
These findings indicated that both vitamin A derivatives induce further survival mechanisms in undernourished intestinal epithelial crypt cells. These mechanisms include increased cell quiescence, decreased apoptosis, increased cell differentiation, and transcription of genes related to MAP kinase signaling pathway.
•Proliferation and apoptosis are impaired by retinyl palmitate in undernourished intestinal epithelial cells.•Vitamin A derivatives induce further survival and differentiation of undernourished intestinal epithelial cells.•MAP kinase signaling pathway via JNK is triggered by vitamin A derivatives in undernourished intestinal epithelial cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33545543</pmid><doi>10.1016/j.nut.2020.111087</doi><orcidid>https://orcid.org/0000-0002-0628-8047</orcidid><orcidid>https://orcid.org/0000-0002-4546-2976</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0899-9007 |
| ispartof | Nutrition (Burbank, Los Angeles County, Calif.), 2021-05, Vol.85, p.111087, Article 111087 |
| issn | 0899-9007 1873-1244 |
| language | eng |
| recordid | cdi_proquest_journals_2510227954 |
| source | Elsevier ScienceDirect Journals |
| subjects | Apoptosis c-Jun protein Cell cycle Cell differentiation Cell growth Cell proliferation Children & youth Crypts Deprivation Developing countries Diarrhea Differentiation (biology) Epithelial cells Epithelium Fatty acid-binding protein Flow cytometry G1 phase Gene expression Genes Glutamine Intestinal epithelium Intestine Kinases LDCs Malnutrition MAP kinase Modulation Necrosis Nutrient deficiency Nutrients Palmitic acid Phases Proteins Public health Retinene Retinoids S phase Signal transduction Signaling Software Transcription factors Undernutrition Vitamin A |
| title | Retinoids delay cell cycle progression and promote differentiation of intestinal epithelial cells exposed to nutrient deprivation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T02%3A49%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Retinoids%20delay%20cell%20cycle%20progression%20and%20promote%20differentiation%20of%20intestinal%20epithelial%20cells%20exposed%20to%20nutrient%20deprivation&rft.jtitle=Nutrition%20(Burbank,%20Los%20Angeles%20County,%20Calif.)&rft.au=de%20Freitas,%20Rosa%20Elayne%20Marques&rft.date=2021-05&rft.volume=85&rft.spage=111087&rft.pages=111087-&rft.artnum=111087&rft.issn=0899-9007&rft.eissn=1873-1244&rft_id=info:doi/10.1016/j.nut.2020.111087&rft_dat=%3Cproquest_cross%3E2510227954%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2510227954&rft_id=info:pmid/33545543&rft_els_id=S0899900720303701&rfr_iscdi=true |