[HTML][HTML] Multi‐omics analysis reveals the regulation of SIRT6 on protein processing of endoplasmic reticulum to alleviate oxidative stress in endothelial cells

P Li, Z Guo, R Feng, N Wu, X Zhong… - Clinical and …, 2022 - ncbi.nlm.nih.gov
P Li, Z Guo, R Feng, N Wu, X Zhong, Z Fang, Y Hu, X Yu, S Zhao, G Zhao, Y He, H Li, J Ge
Clinical and Translational Medicine, 2022ncbi.nlm.nih.gov
To the Editor: Endoplasmic reticulum (ER) is the largest organelle in cells. ER stress is
caused by the protein homeostasis imbalance in ER and contributes to cell dysfunction. 1
SIRT6, a member of sirtuins, participates in DNA repair, metabolism, inflammation and
oxidative stress. 2 However, it is still unclear whether SIRT6 regulates ER stress in
endothelial cells (ECs). In the study, multi-omics approach was used to reveal a novel
mechanism by which SIRT6 alleviated ER stress through maintaining the ER protein …
To the Editor: Endoplasmic reticulum (ER) is the largest organelle in cells. ER stress is caused by the protein homeostasis imbalance in ER and contributes to cell dysfunction. 1 SIRT6, a member of sirtuins, participates in DNA repair, metabolism, inflammation and oxidative stress. 2 However, it is still unclear whether SIRT6 regulates ER stress in endothelial cells (ECs). In the study, multi-omics approach was used to reveal a novel mechanism by which SIRT6 alleviated ER stress through maintaining the ER protein homeostasis.
In view of the important roles of SIRT6 in various cellular functions, human microvascular endothelial cells (HMECs) were genetically engineered to construct four cell lines: SIRT6-kd, SIRT6-kdnc, SIRT6-oe and SIRT6-oenc ECs to explore physiological functions of SIRT6 (Figure S1A). Total 19 835 transcripts, 7120 proteins and 779 metabolites were identified through analysis of transcriptomics, proteomics and metabolomics (Figure 1A–C, Tables S1–3S). The consistency among biological repeats and the divergences among different groups in transcriptomes, proteomes and metabolomes were verified (Figures S1B and S2). The differential genes (fold-change [FC]> 2 or< 0.5 and p-value< 0.05), proteins (FC> 1.2 or< 0.8333 and p-value< 0.05) and metabolites (FC> 1.5 or< 0.67 and p-value< 0.05) were screened (Figure S1C, D). The kd/kdnc up (upregulated) and oe/oenc down (downregulated) genes were combined into SIRT6 downregulated genes (SDGs), and kd/kdnc down and oe/oenc up genes were combined into SIRT6 upregulated genes (SUGs). Similarly, the SIRT6 downregulated proteins (SDPs) and SIRT6 upregulated proteins (SUPs) were obtained with a total of 311 SDGs, 151 SUGs, 529 SDPs and 330 SUPs (Figure 1C). Further, the SDPs, SUPs, SDGs and SUGs were analysed by KEGG enrichment. The results showed that the pathways of ‘protein export’,‘protein processing in endoplasmic reticulum’and ‘ubiquitin-mediated prote-
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