EC Number   |
General Information |
Reference |
|---|
   2.3.1.B41 | malfunction |
minute cholesterol crystals (CCs) significantly suppress SIRT6 expression in endothelial cells. The overexpression of SIRT6 can mitigate minute CC-induced endothelial dysfunction. Expression of Nuclear factor erythroid2-related factor2 (Nrf2) is suppressed after minute CC treatment, whereas SIRT6 overexpression reverses this decrease in Nrf2 expression. Nrf2 activation also notably attenuates minute CC-induced endothelial dysfunction. SIRT6 depletion impairs vascular endothelial function and suppresses Nrf2 expression in hyperlipidemic mice |
756672 |
| 2.3.1.B41 | malfunction |
minute cholesterol crystals (CCs) significantly suppress SIRT6 expression in endothelial cells. The overexpression of SIRT6 can mitigate minute CC-induced endothelial dysfunction. Expression of Nuclear factor erythroid2-related factor2 (Nrf2) is suppressed after minute CC treatment, whereas SIRT6 overexpression reverses this decrease in Nrf2 expression. Nrf2 activation also notably attenuates minute CC-induced endothelial dysfunction. SIRT6 depletion impairs vascular endothelial function and suppresses Nrf2 expression in hyperlipidemic mice. Hearts, livers, spleens, lungs, kidneys and aortas from ecSIRT6-/- mice fed a normal diet do not show obvious pathological differences compared with ecSIRT6+/+ mice. Endothelium-specific SIRT6 knockout further impairs NO synthesis, significantly decreases eNOS activity and suppresses eNOS expression in hyperlipidemic mice. Endothelium-specific SIRT6 knockout further exacerbates endothelial dysfunction in hyperlipidemic mice |
756672 |
| 2.3.1.B41 | malfunction |
overexpression of SIRT6 in astrocytes by itself abrogates the neurotoxic phenotype of amyotrophic lateral sclerosis (ALS) astrocytes. Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons in the spinal cord, brain stem, and motor cortex |
756691 |
| 2.3.1.B41 | malfunction |
overexpression of SIRT6 significantly suppresses TGF-beta1-induced myofibroblast differentiation in HFL1 cells. Mutant SIRT6 (H133Y) without histone deacetylase activity fails to inhibit phosphorylation and nuclear translocation of Smad2. Overexpression of wild-type SIRT6 but not the H133Y mutant inhibits the expression of NF-kappaB-dependent genes including interleukin (IL)-1beta, IL-6 and matrix metalloproteinase-9 (MMP-9) induced by TGF-beta1, all of which have been demonstrated to promote myofibroblast differentiation. SIRT6 overexpression suppresses TGF-beta1-induced Smad2 activation |
757294 |
| 2.3.1.B41 | malfunction |
SIRT6 activity declines with age, with a concomitant accumulation of DNA damage. SIRT6 and its downstream signaling can be targeted in Alzheimer's disease and age related neurodegeneration. Patients with Alzheimer's disease show a remarkable reduction in SIRT6 at both protein and mRNA levels, with further reduction with increased severity of Braak stages. SIRT6KO cells are more sensitive to apoptosis, prevented by GSK3 or ATM inhibition |
756392 |
| 2.3.1.B41 | malfunction |
SIRT6 activity declines with age, with a concomitant accumulation of DNA damage. SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. Brain-specific SIRT6-deficient mice survive, but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death and hyperphosphorylated Tau, a critical mark in several neurodegenerative diseases |
756392 |
| 2.3.1.B41 | malfunction |
SIRT6 deficiency causes major retinal transmission defects concomitant to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells |
730790 |
| 2.3.1.B41 | malfunction |
SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin (Mstn) expression. Upregulation of other factors implicated in muscle atrophy, such as angiotensin-II, activin and Acvr2b, in SIRT6 depleted cells is observed. Effect of SIRT6 deficiency on cardiac expression of muscle-atrophy related genes. Phenotype, detailed overview |
758395 |
| 2.3.1.B41 | malfunction |
SIRT6 depletion in cardiac as well as skeletal muscle cells promotes myostatin (Mstn) expression. Upregulation of other factors implicated in muscle atrophy, such as angiotensin-II, activin and Acvr2b, in SIRT6 depleted cells is observed. SIRT6-KO mice show degenerated skeletal muscle phenotype with significant fibrosis, an effect consistent with increased levels of Mstn. SIRT6 overexpression downregulates the cytokine (TNFalpha-IFNgamma)-induced Mstn expression in C2C12 cells, and promotes myogenesis. SIRT6 overexpression mitigates atrophic effect of tumor-induced cytokines in C2C12 cells. Effect of SIRT6 deficiency on cardiac expression of muscle-atrophy related genes. Phenotype, detailed overview |
758395 |
| 2.3.1.B41 | malfunction |
SIRT6 depletion in cardiac fibroblasts results in increased cell proliferation and extracellular matrix deposition as well as significantly higher expression of alpha-smooth muscle actin, the classical marker of myofibroblast differentiation, and increased formation of focal adhesions. Notably, SIRT6 depletion further exacerbates angiotensin IIinduced myofibroblast differentiation |
739733 |
