Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway

Chandrasekharan, Bindu; Montllor-Albalate, Claudia; Colin, Alyson E.; Andersen, Joshua L.; Jang, Young C.; Reddi, Amit R.

doi:10.1016/j.bbrc.2020.11.011

Cited by 11 publications

(6 citation statements)

References 36 publications

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“…Zinc is a structural constituent of Cu/Zn SOD and is closely related to its activity. Cu/Zn SOD can act as an endogenous antioxidant enzyme and possessed a certain of antioxidant capacity [ 41 , 42 ]. In normal state, cells would produce more SOD to remove superoxide anions, reflected by the increase of the corresponding gene expression.…”

Section: Resultsmentioning

confidence: 99%

Zinc-based metal organic framework with antibacterial and anti-inflammatory properties for promoting wound healing

Chen

Cai

Liu

et al. 2022

Regenerative Biomaterials

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The synergistic effect of antibacterial and anti- inflammatory is needed to overcome the problem of wound healing difficulties. Based on the favorable antibacterial and anti- inflammatory effect of zinc ions (Zn2+) and the physicochemical properties of metal organic frameworks (MOFs), we prepared nanosized zinc-based MOF: Zn-BTC with the ability to slowly release Zn2+. In cellular levels, Zn-BTC possessed lower toxicity to fibroblasts and enhanced capacity of cell proliferation and migration. It also had good bactericidal effect on multiple drug resistant (MDR) bacteria by reducing 41.4% MRSA and 47.2% E. coli. In addition, Zn-BTC also displayed the ability of lowering the expression of antioxidant genes: superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and interleukin 6 (IL6), and enhancing the expression of wound healing genes: transforming growth factors-β (TGF-β) and type I collagen (COL1). Finally, it also demonstrated that Zn-BTC could effectively improve the skin wound healing of SD rats and had no toxicity on major organs. The favorable biocompatibility, antibacterial and anti- inflammatory properties of Zn-BTC gave a new insight of designing novel MOFs for promoting skin wound healing.

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Section: Resultsmentioning

confidence: 99%

Zinc-based metal organic framework with antibacterial and anti-inflammatory properties for promoting wound healing

Chen

Cai

Liu

et al. 2022

Regenerative Biomaterials

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“…(B) Heat map of 53 differentially expressed proteins using PEAKS 10 software (FDR < 0.1, logFC ≥ 1, peptides ≥ 2). (C) Eighteen proteins were identified to have a connection to Wnt signaling in the literature: Fabp3 87 , Aldh2.2 88 , Prdx1 75 , Idhba 89 , Pcxa 90 , Tcp1 91 , Igf2bp3 92 , Pkma 93 , Actb2 94 , Cct5 95 , Prdx6 96 , Tpi1a 97 , Prdx2 76 , Ppa1b 98 , Sod1 99 , Cox17 100 , Ranbp1 101 , Stmn1a 102 . (D-E) String protein networks were created using all proteins identified (D) and a network of the 39 non ribosomal proteins (E).…”

Section: Resultsmentioning

confidence: 99%

Loss of Nkd1 is epistatic to loss of Axin2 in regulating Wnt signaling

Bell,

Khan,

Stutt

et al. 2023

Preprint

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Wnt signaling is a crucial developmental pathway involved in early development as well as stem cell maintenance in adults and its misregulation leads to numerous diseases. Thus, understanding the regulation of this pathway becomes vitally important. Axin2 and Nkd1 are widely utilized negative feedback regulators in Wnt signaling where Axin2 functions to destabilize cytoplasmic β-catenin, and Nkd1 functions to inhibit the nuclear localization of β-catenin. Here, we set out to further understand how Axin2 and Nkd1 regulate Wnt signaling by creatingaxin2-/-,nkd1-/-single mutants andaxin2-/-;nkd1-/-double mutant zebrafish using sgRNA/Cas9. All three Wnt regulator mutants were viable and had impaired heart looping, neuromast migration defects, and behavior abnormalities in common, but there were no signs of synergy in theaxin2-/-;nkd1-/-double mutants. Further, Wnt target gene expression by qRT-PCR, and RNA-seq analysis and protein expression by mass spectrometry demonstrated that the doubleaxin2-/-;nkd1-/-mutant resembled thenkd1-/-phenotype demonstrating that Axin2 functions upstream of Nkd1 and that loss of Nkd1 is dominant over the loss of Axin2. In support of this, the data further demonstrates that Axin2 uniquely alters the properties of β-catenin-dependent transcription having novel readouts of Wnt activity compared tonkd1-/-or theaxin2-/-;nkd1-/-double mutant. We also tested the sensitivity of the Wnt regulator mutants to exacerbated Wnt signaling, where the single mutants displayed characteristic heightened Wnt sensitivity, resulting in an eyeless phenotype. Surprisingly, this phenotype was rescued in the double mutant, where we speculate that cross-talk between Wnt/β-catenin and Wnt/Planar Cell Polarity pathways could lead to altered Wnt signaling in some scenarios. Collectively, the data emphasizes both the commonality and the complexity in the feedback regulation of Wnt signaling.

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“… 67 In a mammalian cell line, a partly analogous mechanism involving the stabilization of casein kinase 1-y has been suggested to be essential for the Wnt signalling pathway. 68 Moreover, oxidative stress has been found to lead to phosphorylation of serines in SOD1 in complex with the effector kinase Dun1 in yeast. 69 After translocation to the nucleus, phosphorylated SOD1 binds to promoters regulating the expression of oxidative resistance and repair genes.…”

Section: Discussionmentioning

confidence: 99%

The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1

Park

Nordström

Tsiakas

et al. 2022

Brain Communications

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Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain of function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile onset motor neuron disease. We explored the bodily effects of Superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs*11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs*11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, nonneuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted Infantile Superoxide dismutase-1 Deficiency Syndrome.

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Cu/Zn Superoxide Dismutase (Sod1) regulates the canonical Wnt signaling pathway

Cited by 11 publications

References 36 publications

Zinc-based metal organic framework with antibacterial and anti-inflammatory properties for promoting wound healing

Zinc-based metal organic framework with antibacterial and anti-inflammatory properties for promoting wound healing

Loss of Nkd1 is epistatic to loss of Axin2 in regulating Wnt signaling

The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1

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