Related Experiment Video
Updated: Jan 5, 2026
Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis
Published on: January 5, 2017
Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative
Meng-Ting Ren1, Meng-Li Gu2, Xin-Xin Zhou3
1Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Background:
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing.
Aim:
To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms.
Methods:
We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of occludin and zona occludens 1 (ZO-1) was assessed by Western blot analysis. Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis. Dextran sodium sulfate (DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d. Transferase-mediated dUTP nick-end labeling (TUNEL) assays were conducted to assess apoptosis in colon tissues. The expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot.
Results:
SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis, whereas NAM administration caused the opposite effects. DSS-induced colitis mice treated with SRT1720 had a lower disease activity index (P < 0.01), histological score (P < 0.001), inflammatory cytokine levels (P < 0.01), and apoptotic cell rate (P < 0.01), while exposure to NAM caused the opposite effects. Moreover, SIRT1 activation reduced the expression levels of GRP78, CHOP, cleaved caspase-12, cleaved caspase-9, and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice.
Conclusion:
SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12. SIRT1 activation may be a potential therapeutic strategy for UC.
Insights
Sirtuin 1 (SIRT1) activation protects intestinal epithelial cells from apoptosis, offering a potential therapeutic strategy for ulcerative colitis (UC). This study shows SIRT1 reduces endoplasmic reticulum stress markers and improves colitis in mice.
Area of Science:
- Molecular Biology
- Cell Biology
- Gastroenterology
Background:
- Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, is implicated in various diseases but its role in ulcerative colitis (UC) remains unclear.
- Investigating SIRT1's function in intestinal epithelial cells (IECs) is crucial for understanding UC pathogenesis.
Purpose of the Study:
- To elucidate the role of SIRT1 in IECs during UC.
- To explore the underlying molecular mechanisms of SIRT1's action in UC.
Main Methods:
- A co-culture model of macrophages and Caco-2 cells was established.
- SIRT1 activator (SRT1720) and inhibitor (nicotinamide) were used to assess occludin, ZO-1 expression, and apoptosis.
- Dextran sodium sulfate (DSS)-induced colitis mouse models were treated with SRT1720 or nicotinamide to evaluate disease activity, histology, cytokine levels, and apoptosis.
Main Results:
- SRT1720 treatment increased occludin and ZO-1 levels while inhibiting Caco-2 cell apoptosis; nicotinamide had opposite effects.
- In DSS-induced colitis mice, SRT1720 reduced disease activity, histological scores, inflammatory cytokines, and apoptosis rates, whereas nicotinamide worsened these parameters.
- SIRT1 activation decreased endoplasmic reticulum stress markers (GRP78, CHOP) and apoptosis-related molecules (caspase-12, -9, -3) in both cell and mouse models.
Conclusions:
- SIRT1 activation mitigates IEC apoptosis by suppressing endoplasmic reticulum stress-mediated pathways involving CHOP and caspase-12.
- SIRT1 activation demonstrates therapeutic potential for ulcerative colitis.
Related Concept Videos
01:31Regulation of the Unfolded Protein Response
01:23Renewal of Intestinal Stem Cells
01:17Role of ER in the Secretory Pathway
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:37The Unfolded Protein Response