1 Ocak 2020 Dergi makalesi Açık Erişim

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

Citation Style Language JSON

{
  "DOI": "10.1007/s11033-020-05665-3", 
  "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.", 
  "author": [
    {
      "family": "Sermikli", 
      "given": " Benan Pelin"
    }, 
    {
      "family": "Aydogdu", 
      "given": " Gulizar"
    }, 
    {
      "family": "Yilmaz", 
      "given": " Erkan"
    }
  ], 
  "container_title": "MOLECULAR BIOLOGY REPORTS", 
  "id": "9551", 
  "issue": "8", 
  "issued": {
    "date-parts": [
      [
        2020, 
        1, 
        1
      ]
    ]
  }, 
  "page": "5927-5942", 
  "title": "Role of the O-GlcNAc modification on insulin resistance and endoplasmic reticulum stress in 3T3-L1 cells", 
  "type": "article-journal", 
  "volume": "47"
}