L-carnitine cause to increase cell proliferation of C-Kit+ hematopoietic progenitor cells via decreasing the PI3K and FOXO-1 protein expression
Stem cell-based therapy has emerged as an attractive approach for regenerative medicine. Poor survival and maintenance of the cells used in regenerative medicine are considered as serious barriers to enhance the efficacy of the cell therapy. Using some antioxidants has been reported to prevent the a...
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description | Stem cell-based therapy has emerged as an attractive approach for regenerative medicine. Poor survival and maintenance of the cells used in regenerative medicine are considered as serious barriers to enhance the efficacy of the cell therapy. Using some antioxidants has been reported to prevent the aging of stem cells, and finding effective factors to reduce the senescence of these cells has impressive potential in cell therapy. The PI3K pathway adversely regulates the transcription factors known as FOXO, which are thought to have an inhibitory influence on cell proliferation. By downregulating FOXO and other targets, PI3K signaling controls the growth of cells. For this reason, the aim of the present study is to investigate the effect of L-carnitine (LC) as antioxidant on the cell proliferation and the protein expression of PI3K and FOXO.
For understanding the in vitro effect of LC on the PI3K and FOXO-1 expression of C-kit+ hematopoietic progenitor cells, the bone marrow mononuclear cells were isolated, and C-kit+ cells was enriched by the magnetic-activated cell sorting (MACS). Next, the identification of enriched C-kit+ cells were done by flowcytometry and immunocytochemistry. Then, C-kit+ cells were treated with 0.2 mM LC, the cells were collected at the end of the treatment period (48 h), and the proteins were extracted. In the following, the protein expression of PI3K and FOXO-1 was measured by western blotting. In addition, flowcytometry was done to assess the Ki-67 expression as a key marker for cell proliferation investigation.
0.2 mM LC cause to significantly decrease in the protein expression of PI3K and FOXO-1 (*P |
doi_str_mv | 10.1016/j.tice.2024.102558 |
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For understanding the in vitro effect of LC on the PI3K and FOXO-1 expression of C-kit+ hematopoietic progenitor cells, the bone marrow mononuclear cells were isolated, and C-kit+ cells was enriched by the magnetic-activated cell sorting (MACS). Next, the identification of enriched C-kit+ cells were done by flowcytometry and immunocytochemistry. Then, C-kit+ cells were treated with 0.2 mM LC, the cells were collected at the end of the treatment period (48 h), and the proteins were extracted. In the following, the protein expression of PI3K and FOXO-1 was measured by western blotting. In addition, flowcytometry was done to assess the Ki-67 expression as a key marker for cell proliferation investigation.
0.2 mM LC cause to significantly decrease in the protein expression of PI3K and FOXO-1 (*P<0.05 and **P<0.01, respectively). Also, the expression of Ki-67 was significantly increased in the presence of 0.2 mM LC (***P<0.001).
Briefly, LC can be considered an effective factor in increasing the proliferation of C-kit+ cells via some signaling pathways.
•Aging causes reduced HSC function as well as self-renewal ability.•LC could be considered a suitable antioxidant for ameliorating the aging of C-kit+ HSCs.•The effect of LC on aging of C-kit+ HSCs via decreasing PI3K/FOXO protein as components of the aging-dependent pathway.</description><identifier>ISSN: 0040-8166</identifier><identifier>ISSN: 1532-3072</identifier><identifier>EISSN: 1532-3072</identifier><identifier>DOI: 10.1016/j.tice.2024.102558</identifier><identifier>PMID: 39260072</identifier><language>eng</language><publisher>Scotland: Elsevier Ltd</publisher><subject>Aging ; Animals ; C-kit+ hematopoietic progenitor cells ; Carnitine - pharmacology ; Cell Proliferation - drug effects ; Clinical agent ; Forkhead Box Protein O1 - metabolism ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - drug effects ; Hematopoietic Stem Cells - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-kit - metabolism ; Regenerative medicine ; Signal Transduction - drug effects</subject><ispartof>Tissue & cell, 2024-12, Vol.91, p.102558, Article 102558</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c237t-47946f39a1e80f4b8e432c4aa8d60069382d25285136287ddd1e326cd70221c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0040816624002593$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39260072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valipour, Behnaz</creatorcontrib><creatorcontrib>Fathi, Ezzatollah</creatorcontrib><creatorcontrib>Farahzadi, Raheleh</creatorcontrib><creatorcontrib>Naderali, Elahe</creatorcontrib><creatorcontrib>Behniafar, Hamed</creatorcontrib><title>L-carnitine cause to increase cell proliferation of C-Kit+ hematopoietic progenitor cells via decreasing the PI3K and FOXO-1 protein expression</title><title>Tissue & cell</title><addtitle>Tissue Cell</addtitle><description>Stem cell-based therapy has emerged as an attractive approach for regenerative medicine. Poor survival and maintenance of the cells used in regenerative medicine are considered as serious barriers to enhance the efficacy of the cell therapy. Using some antioxidants has been reported to prevent the aging of stem cells, and finding effective factors to reduce the senescence of these cells has impressive potential in cell therapy. The PI3K pathway adversely regulates the transcription factors known as FOXO, which are thought to have an inhibitory influence on cell proliferation. By downregulating FOXO and other targets, PI3K signaling controls the growth of cells. For this reason, the aim of the present study is to investigate the effect of L-carnitine (LC) as antioxidant on the cell proliferation and the protein expression of PI3K and FOXO.
For understanding the in vitro effect of LC on the PI3K and FOXO-1 expression of C-kit+ hematopoietic progenitor cells, the bone marrow mononuclear cells were isolated, and C-kit+ cells was enriched by the magnetic-activated cell sorting (MACS). Next, the identification of enriched C-kit+ cells were done by flowcytometry and immunocytochemistry. Then, C-kit+ cells were treated with 0.2 mM LC, the cells were collected at the end of the treatment period (48 h), and the proteins were extracted. In the following, the protein expression of PI3K and FOXO-1 was measured by western blotting. In addition, flowcytometry was done to assess the Ki-67 expression as a key marker for cell proliferation investigation.
0.2 mM LC cause to significantly decrease in the protein expression of PI3K and FOXO-1 (*P<0.05 and **P<0.01, respectively). Also, the expression of Ki-67 was significantly increased in the presence of 0.2 mM LC (***P<0.001).
Briefly, LC can be considered an effective factor in increasing the proliferation of C-kit+ cells via some signaling pathways.
•Aging causes reduced HSC function as well as self-renewal ability.•LC could be considered a suitable antioxidant for ameliorating the aging of C-kit+ HSCs.•The effect of LC on aging of C-kit+ HSCs via decreasing PI3K/FOXO protein as components of the aging-dependent pathway.</description><subject>Aging</subject><subject>Animals</subject><subject>C-kit+ hematopoietic progenitor cells</subject><subject>Carnitine - pharmacology</subject><subject>Cell Proliferation - drug effects</subject><subject>Clinical agent</subject><subject>Forkhead Box Protein O1 - metabolism</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-kit - metabolism</subject><subject>Regenerative medicine</subject><subject>Signal Transduction - drug effects</subject><issn>0040-8166</issn><issn>1532-3072</issn><issn>1532-3072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9rVDEUxYModqx-AReSpSBvTG7y_oEbGdpaWhgXCu5CmtzX3mEmGZNMqZ_Cr2xep7p0leRyzo9zcxh7K8VSCtl93CwLOVyCAF0H0LbDM7aQrYJGiR6es4UQWjSD7LoT9irnjRCi17J_yU7UCF19wIL9vm6cTYEKBeTOHjLyEjkFl9DWu8Ptlu9T3NKEyRaKgceJr5orKh_4He5siftIWHPMqlusoJgeXZnfk-UeH0EUbnm5Q_71Ul1xGzw_X_9YN3L2FKTA8WGfMOeKf81eTHab8c3Tecq-n599W31prtcXl6vPNS2ovjS6H3U3qdFKHMSkbwbUCpy2dvB1sW5UA3hoYWil6mDovfcSFXTO9wJAulGdsvdHbo3w84C5mB3lObcNGA_ZKCmU1q1o-yqFo9SlmHPCyewT7Wz6ZaQwcxFmY-YizFyEORZRTe-e-IebHfp_lr8_XwWfjgKsW94TJpMdYXDoKaErxkf6H_8P1yGZYQ</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Valipour, Behnaz</creator><creator>Fathi, Ezzatollah</creator><creator>Farahzadi, Raheleh</creator><creator>Naderali, Elahe</creator><creator>Behniafar, Hamed</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>202412</creationdate><title>L-carnitine cause to increase cell proliferation of C-Kit+ hematopoietic progenitor cells via decreasing the PI3K and FOXO-1 protein expression</title><author>Valipour, Behnaz ; Fathi, Ezzatollah ; Farahzadi, Raheleh ; Naderali, Elahe ; Behniafar, Hamed</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c237t-47946f39a1e80f4b8e432c4aa8d60069382d25285136287ddd1e326cd70221c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aging</topic><topic>Animals</topic><topic>C-kit+ hematopoietic progenitor cells</topic><topic>Carnitine - pharmacology</topic><topic>Cell Proliferation - drug effects</topic><topic>Clinical agent</topic><topic>Forkhead Box Protein O1 - metabolism</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - drug effects</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-kit - metabolism</topic><topic>Regenerative medicine</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valipour, Behnaz</creatorcontrib><creatorcontrib>Fathi, Ezzatollah</creatorcontrib><creatorcontrib>Farahzadi, Raheleh</creatorcontrib><creatorcontrib>Naderali, Elahe</creatorcontrib><creatorcontrib>Behniafar, Hamed</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Tissue & cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valipour, Behnaz</au><au>Fathi, Ezzatollah</au><au>Farahzadi, Raheleh</au><au>Naderali, Elahe</au><au>Behniafar, Hamed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>L-carnitine cause to increase cell proliferation of C-Kit+ hematopoietic progenitor cells via decreasing the PI3K and FOXO-1 protein expression</atitle><jtitle>Tissue & cell</jtitle><addtitle>Tissue Cell</addtitle><date>2024-12</date><risdate>2024</risdate><volume>91</volume><spage>102558</spage><pages>102558-</pages><artnum>102558</artnum><issn>0040-8166</issn><issn>1532-3072</issn><eissn>1532-3072</eissn><abstract>Stem cell-based therapy has emerged as an attractive approach for regenerative medicine. Poor survival and maintenance of the cells used in regenerative medicine are considered as serious barriers to enhance the efficacy of the cell therapy. Using some antioxidants has been reported to prevent the aging of stem cells, and finding effective factors to reduce the senescence of these cells has impressive potential in cell therapy. The PI3K pathway adversely regulates the transcription factors known as FOXO, which are thought to have an inhibitory influence on cell proliferation. By downregulating FOXO and other targets, PI3K signaling controls the growth of cells. For this reason, the aim of the present study is to investigate the effect of L-carnitine (LC) as antioxidant on the cell proliferation and the protein expression of PI3K and FOXO.
For understanding the in vitro effect of LC on the PI3K and FOXO-1 expression of C-kit+ hematopoietic progenitor cells, the bone marrow mononuclear cells were isolated, and C-kit+ cells was enriched by the magnetic-activated cell sorting (MACS). Next, the identification of enriched C-kit+ cells were done by flowcytometry and immunocytochemistry. Then, C-kit+ cells were treated with 0.2 mM LC, the cells were collected at the end of the treatment period (48 h), and the proteins were extracted. In the following, the protein expression of PI3K and FOXO-1 was measured by western blotting. In addition, flowcytometry was done to assess the Ki-67 expression as a key marker for cell proliferation investigation.
0.2 mM LC cause to significantly decrease in the protein expression of PI3K and FOXO-1 (*P<0.05 and **P<0.01, respectively). Also, the expression of Ki-67 was significantly increased in the presence of 0.2 mM LC (***P<0.001).
Briefly, LC can be considered an effective factor in increasing the proliferation of C-kit+ cells via some signaling pathways.
•Aging causes reduced HSC function as well as self-renewal ability.•LC could be considered a suitable antioxidant for ameliorating the aging of C-kit+ HSCs.•The effect of LC on aging of C-kit+ HSCs via decreasing PI3K/FOXO protein as components of the aging-dependent pathway.</abstract><cop>Scotland</cop><pub>Elsevier Ltd</pub><pmid>39260072</pmid><doi>10.1016/j.tice.2024.102558</doi></addata></record> |
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subjects | Aging Animals C-kit+ hematopoietic progenitor cells Carnitine - pharmacology Cell Proliferation - drug effects Clinical agent Forkhead Box Protein O1 - metabolism Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - drug effects Hematopoietic Stem Cells - metabolism Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-kit - metabolism Regenerative medicine Signal Transduction - drug effects |
title | L-carnitine cause to increase cell proliferation of C-Kit+ hematopoietic progenitor cells via decreasing the PI3K and FOXO-1 protein expression |
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