The role of different SIRT1-mediated signaling pathways in toxic injury

Abstract

Common environmental pollutants and drugs encountered in everyday life can cause toxic damage to the body through oxidative stress, inflammatory stimulation, induction of apoptosis, and inhibition of energy metabolism. Silent information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, is a member of the evolutionarily highly conserved Sir2 (silent information regulator 2) superprotein family, which is located in the nucleus and cytoplasm. It can deacetylate protein substrates in various signal transduction pathways to regulate gene expression, cell apoptosis and senescence, participate in the process of neuroprotection, energy metabolism, inflammation and the oxidative stress response in living organisms, and plays an important role in toxic damage caused by toxicants and in the process of SIRT1 activator/inhibitor antagonized toxic damage. This review summarizes the role that SIRT1 plays in toxic damage caused by toxicants via its interactions with protein substrates in certain signaling pathways.

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

“…Activated SIRT1 deacetylates and affects the activity of both members of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/estrogen-related receptor alpha (PGC1α/ERRα) complex and FOXO1/3, which are essential metabolism regulatory transcription factors [162,163]. SIRT1 uses first pathway, PGC1α/ERRα, so as to induce nuclear factor erythroid 2-related factor 2 (Nrf2), yet, it is also capable of direct activation of Nrf2 using numerous mechanisms [164]. The latter negatively impacts on proinflammatory cytokines (e.g., TNF-α, IL-1) and acts as a master regulator of mitochondrial biogenesis and transcription of genes possesing ARE (antioxidant response elements) (e.g., CAT, GPx, heme oxygenenase (HO-1), SOD1/2, GSH, peroxiredoxin 3/5 (PRDX3/5), thioredoxin-interacting protein (TXNIP), NAD(P)H-quinone oxidoreductase 1 (NQO1), glutathione S-transferases (GSTs), glutamate-cysteine ligase modifier subunit (GCLM), cysteine ligase catalytic subunit (GCLC), glucose-6-phosphate dehydrogenase (G6PD)) [164][165][166][167].…”

Urinary Exosomal MiRNA-4534 as a Novel Diagnostic Biomarker for Diabetic Kidney Disease

“…Studies have shown ( 29 ) that miR-4534 is overexpressed in prostate cancer (PCA) and blocks cell proliferation, migration, induce G0/G1 cell cycle arrest and apoptosis, thus affecting tumor tissue growth, which may provide a therapeutic target and mechanism for the treatment of PCA in the future. In order to further explore the pathogenesis of DKD, our research group obtained a KEGG pathway map of miR-4534 through bioinformatics analysis ( Figure 8 ), of which SIRT1/FOXO signaling pathway ( 30 ) is most closely related to DKD. It is well-known that studies on the pathogenesis of DKD are increasingly focused on inflammatory responses ( 31 ), and FOXO is one of the most well-known pathways.…”

Interaction of Sirtuin 1 (SIRT1) Candidate Longevity Gene and Particulate Matter (PM2.5) on All-cause Mortality: a Longitudinal Cohort Study in China

“…Studies indicate genetic susceptibility is likely to play a role in response to air pollution, especially on cardiovascular and respiratory outcomes [30]. A recent review indicated that SIRT1 plays in toxicological damage caused by environmental toxicants such as PM 2.5 , the PM-induced injury affects SIRT1 expression, which then affects the expression and activity of downstream proteins, resulting in toxic damage [42]. In addition, one molecular biology nding suggested that PM 2.5 can upregulate MicroRNA-146a-3p and induces the in ammatory macrophage polarization by targeting SIRT1 [43].…”