SIRT1

Case study 1: Lili Lian, 2023

To determine whether SIRT1 regulates high glucose (HG)-induced inflammation and cataract formation through modulating TXNIP/NLRP3 inflammasome activation in human lens epithelial cells (HLECs) and rat lenses. HG stress from 25 to 150 mM was imposed on HLECs, with treatments using small interfering RNAs (siRNAs) targeting NLRP3, TXNIP, and SIRT1, as well as a lentiviral vector (LV) for SIRT1. Rat lenses were cultivated with HG media, with or without the addition of NLRP3 inhibitor MCC950 or SIRT1 agonist SRT1720. Western blots, and immunofluorescent staining evaluated the mRNA and protein levels of SIRT1, TXNIP, NLRP3, ASC, and IL-1β.

HG stress induced a decline in SIRT1 expression. Transfections of si-SIRT1 and LV-SIRT1 exerted inverse effects on NLRP3 inflammasome activation, suggesting that SIRT1 acts as an upstream regulator of TXNIP/NLRP3 activity. The TXNIP/NLRP3 inflammasome pathway promotes HG-induced inflammation and HLEC pyroptosis, which is negatively regulated by SIRT1.

Fig1. HLECs were transfected with control or NLRP3 siRNAs for 72 hours. Cells were lysed and immunoblotted with antibodies against SIRT1, TXNIP, NLRP3, and β-actin.

Fig2. Overexpression of SIRT1 suppresses TXNIP/NLRP3 inflammasome activation.

Case study 2: Lars Erichsen, 2022

The aging process is manifested by a multitude of inter-linked biological processes. These processes contribute to genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, de-regulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. The mammalian ortholog of the yeast silent information regulator (Sir2) SIRT1 is a NAD+-dependent class III histone deacetylase and has been recognized to be involved in many of the forementioned processes.

SIX2-positive urine derived renal progenitor cells-UdRPCs isolated directly from human urine show typical hallmarks of aging. This includes the subsequent transcriptional downregulation of SIRT1 and its downstream targets AKT and GSK3β with increased donor age. The researchers provide evidence that the renal progenitor transcription factor SIX2 binds to the coding sequence of SIRT1. Furthermore, they show that the SIRT1 promoter region is methylation sensitive and becomes methylated during aging, dividing them into SIRT1-high and -low expressing UdRPCs.

Fig3. Relative protein expression normalized to β-ACTIN for SIRT1, AKT and GSK3β and relative protein phosphorylation for AKT, GSK3β and pH2A.X was detected by Western blot.

Fig4. Relative protein expression normalized to β-ACTIN for SIRT1, AKT and GSK3β and relative protein phosphorylation for AKT, GSK3β and pH2A.X was detected by Western blotting.

Fig1. Non-apoptotic doses of CDDP downregulate the expression of SIRT1 in oral cancer and CDDP-resistance oral cancer-derived PGCCs. (Srimanta Patra, 2023)

Fig2. SIRT1 inhibits the cell senescence-associated secretory phenotype (SASP; secretion of IL-6, IL-1β, and MMPs) by regulating the SIRT1/NF-κB and SIRT1/JNK pathways, thereby alleviating the inflammatory response. (Chaoqun Sun, 2023)

SIRT1 involved in several pathways and played different roles in them. We selected most pathways SIRT1 participated on our site, such as FoxO signaling pathway, AMPK signaling pathway, MicroRNAs in cancer, which may be useful for your reference. Also, other proteins which involved in the same pathway with SIRT1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

SIRT1 has several biochemical functions, for example, HLH domain binding, NOT NAD+ ADP-ribosyltransferase activity, NAD+ binding. Some of the functions are cooperated with other proteins, some of the functions could acted by SIRT1 itself. We selected most functions SIRT1 had, and list some proteins which have the same functions with SIRT1. You can find most of the proteins on our site.

SIRT1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with SIRT1 here. Most of them are supplied by our site. Hope this information will be useful for your research of SIRT1.

TP53; WRN