1 Ocak 2020 Dergi makalesi Açık Erişim

Sermikli, Benan Pelin; Aydogdu, Gulizar; Yilmaz, Erkan

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  <identifier identifierType="URL">https://aperta.ulakbim.gov.tr/record/9551</identifier>
  <creators>
    <creator>
      <creatorName>Sermikli, Benan Pelin</creatorName>
      <givenName>Benan Pelin</givenName>
      <familyName>Sermikli</familyName>
    </creator>
    <creator>
      <creatorName>Aydogdu, Gulizar</creatorName>
      <givenName>Gulizar</givenName>
      <familyName>Aydogdu</familyName>
    </creator>
    <creator>
      <creatorName>Yilmaz, Erkan</creatorName>
      <givenName>Erkan</givenName>
      <familyName>Yilmaz</familyName>
      <affiliation>Ankara Univ, Biotechnol Inst, Ankara, Turkey</affiliation>
    </creator>
  </creators>
  <titles>
    <title>Role Of The O-Glcnac Modification On Insulin Resistance And Endoplasmic Reticulum Stress In 3T3-L1 Cells</title>
  </titles>
  <publisher>Aperta</publisher>
  <publicationYear>2020</publicationYear>
  <dates>
    <date dateType="Issued">2020-01-01</date>
  </dates>
  <resourceType resourceTypeGeneral="Text">Journal article</resourceType>
  <alternateIdentifiers>
    <alternateIdentifier alternateIdentifierType="url">https://aperta.ulakbim.gov.tr/record/9551</alternateIdentifier>
  </alternateIdentifiers>
  <relatedIdentifiers>
    <relatedIdentifier relatedIdentifierType="DOI" relationType="IsIdenticalTo">10.1007/s11033-020-05665-3</relatedIdentifier>
  </relatedIdentifiers>
  <rightsList>
    <rights rightsURI="http://www.opendefinition.org/licenses/cc-by">Creative Commons Attribution</rights>
    <rights rightsURI="info:eu-repo/semantics/openAccess">Open Access</rights>
  </rightsList>
  <descriptions>
    <description descriptionType="Abstract">O-linkedN-acetyl-glucosamine (O-GlcNAc) is a post-translational protein modification that regulates cell signaling and involves in several pathological conditions. O-GlcNAc transferase (OGT) catalyzes the attachment, while O-GlcNAcase (OGA) splits the GlcNAc molecules from the serine or threonine residues of the nuclear and cellular proteins. The hexosamine biosynthesis pathway (HBP) is a small branch of glycolysis that provides a substrate for the OGT and serves as a nutrient sensor. In this study, we investigated the impact of external O-GlcNAc modification stimulus on the insulin signal transduction, unfolded protein response, and HBP in 3T3-L1 cells. First, we treated cells with glucosamine and PUGNAc to stimulate the O-GlcNAcylation of total proteins. Also, we treated cells with tunicamycin as a positive internal control, which is a widely-used endoplasmic reticulum stressor. We used two in vitro models to understand the impact of the cellular state of insulin sensibility on this hypothesis. So, we employed insulin-sensitive preadipocytes and insulin-resistant adipocytes to answer these questions. Secondly, the OGT-silencing achieved in the insulin-resistant preadipocyte model by using the short-hairpin RNA (shRNA) interference method. Thereafter, the cells treated with the above-mentioned compounds to understand the role of the diminished O-GlcNAc protein modification on the insulin signal transduction, unfolded protein response, and HBP. We found that elevated O-GlcNAcylation of the total proteins displayed a definite correlation in insulin resistance and endoplasmic reticulum stress. Furthermore, we identified that the degree of this correlation depends on the cellular state of insulin sensitivity. Moreover, reduced O-GlcNAcylation of the total proteins by the shRNA-mediated silencing of the OGT gene, which is the only gene to modify proteins with the O-GlcNAc molecule, reversed the insulin resistance and endoplasmic reticulum stress phenotype, even with the externally stimulated O-GlcNAc modification conditions. In conclusion, our results suggest that OGT regulates insulin receptor signaling and unfolded protein response by modulating O-GlcNAc levels of total proteins, in response to insulin resistance. Therefore, it can be a potential therapeutic target to prevent insulin resistance and endoplasmic reticulum stress.</description>
  </descriptions>
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