SOD1, more than just an antioxidant

Eleuthério, Elis C. A.; Magalhães, Rayne Stfhany Silva; Brasil, Aline de Araújo; Neto, José Raphael Monteiro; Paranhos, Luan de Holanda

doi:10.1016/j.abb.2020.108701

Cited by 130 publications

(76 citation statements)

References 179 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanisms by which mutant SOD1 proteins cause cell death in patients are still unclear. Various mechanisms have been suggested, such as participation of oxidative stress, abnormal protein aggregation rich in ubiquitin/ubiquitin-like proteins, and disrupted axonal transport and mitochondrial dysfunction [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation

Dangoumau

Marouillat

Coelho

et al. 2021

IJMS

View full text Add to dashboard Cite

Protein aggregates in affected motor neurons are a hallmark of amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to their formation remain incompletely understood. Oxidative stress associated with age, the major risk factor in ALS, contributes to this neurodegeneration in ALS. We show that several genes coding for enzymes of the ubiquitin and small ubiquitin-related modifier (SUMO) pathways exhibit altered expression in motor neuronal cells exposed to oxidative stress, such as the CCNF gene mutated in ALS patients. Eleven of these genes were further studied in conditions combining oxidative stress and the expression of an ALS related mutant of the superoxide dismutase 1 (SOD1) gene. We observed a combined effect of these two environmental and genetic factors on the expression of genes, such as Uhrf2, Rbx1, Kdm2b, Ube2d2, Xaf1, and Senp1. Overall, we identified dysregulations in the expression of enzymes of the ubiquitin and SUMO pathways that may be of interest to better understand the pathophysiology of ALS and to protect motor neurons from oxidative stress and genetic alterations.

show abstract

Section: Introductionmentioning

confidence: 99%

Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation

Dangoumau

Marouillat

Coelho

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…The activity of three essential markers implicated in cellular response to oxidative stress was evaluated in vivo after ENs acute exposure. SOD1 is an antioxidant enzyme which regulates the superoxide levels from cytosol and mitochondrial intermembrane [ 39 ]. It has been observed that its deletion is related to ROS production and the reduction of antioxidant enzymes activities in colon tissues, agreeing with the downregulation observed in the present research [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Changes after Enniatins A, A1, B and B1 Ingestion in Rat Stomach, Liver, Kidney and Lower Intestine

Cimbalo

Alonso-Garrido

Font

et al. 2021

Foods

View full text Add to dashboard Cite

Enniatins (ENs) are depsipeptide mycotoxins produced by Fusarium fungi. They are known for their capacity to modulate cell membrane permeability and disruption of ionic gradients, affecting cell homeostasis and initiating oxidative stress mechanisms. The effect of the acute toxicity of ENs A, A1, B and B1 at two different concentrations after 8 h of exposure was analysed in Wistar rats by a transcriptional approach. The following key mitochondrial and nuclear codified genes related to the electron transport chain were considered for gene expression analysis in stomach, liver, kidney and lower intestine by quantitative Real-Time PCR: mitochondrially encoded NADH dehydrogenase 1 (MT-ND1), mitochondrially encoded cytochrome c oxidase 1 (MT-COX1), succinate dehydrogenase flavoprotein subunit A and ATP synthase F1 subunit alpha, respectively. Moreover, the expression of markers involved in oxidative stresssuperoxide dismutase 1 (SOD1), glutathione peroxidase 1 (Gpx1), heme oxygenase 1, apoptosis B-cell lymphoma 2, Bcl2 Associated protein X (Bax), tumor suppressor protein (p53), inhibition of apoptosis nuclear factor kappa of activated B cells, immune system interleukin 1β and intestinal tight junction Occludin merely in lower intestine tissues have been investigated. For mitochondrial genes, the main differences were observed for MT-ND1 and MT-COX1, showing its deficiency in all selected organs. With regard to the intestinal barrier’s cellular response to oxidative stress, the activity of the antioxidant gene SOD1 was decreased in a dose-dependent manner. Similarly, the catalytic enzyme GPx1 was also downregulated though merely at medium dose employed. On the contrary, the pro-apoptotic Bax and p53 regulators were activated after ENs exposure, reporting a significant increase in their expression. Furthermore, the alteration of intestinal permeability was assessed by the abnormal activity of the tight junction protein occludin. In summary, ENs may generate mitochondrial disorders and induce oxidative stress in intestinal barrier function.

show abstract

“…In this context, ion homeostasis failure caused by SOD1 loss might induce age-related pathological changes in vivo and in vitro. Recently, several studies reported that SOD1 protein induces post-translational modifications and regulates the expression of antioxidant genes as a transcriptional factor [54]. In addition to the loss of antioxidant activity, the loss of the metal chelating ability and transcriptional function might markedly affect Sod1-deficient phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice

Watanabe

Shibuya

Ozawa

et al. 2021

IJMS

View full text Add to dashboard Cite

Intracellular superoxide dismutases (SODs) maintain tissue homeostasis via superoxide metabolism. We previously reported that intracellular reactive oxygen species (ROS), including superoxide accumulation caused by cytoplasmic SOD (SOD1) or mitochondrial SOD (SOD2) insufficiency, induced p53 activation in cells. SOD1 loss also induced several age-related pathological changes associated with increased oxidative molecules in mice. To evaluate the contribution of p53 activation for SOD1 knockout (KO) (Sod1−/−) mice, we generated SOD1 and p53 KO (double-knockout (DKO)) mice. DKO fibroblasts showed increased cell viability with decreased apoptosis compared with Sod1−/− fibroblasts. In vivo experiments revealed that p53 insufficiency was not a great contributor to aging-like tissue changes but accelerated tumorigenesis in Sod1−/− mice. Furthermore, p53 loss failed to improve dilated cardiomyopathy or the survival in heart-specific SOD2 conditional KO mice. These data indicated that p53 regulated ROS-mediated apoptotic cell death and tumorigenesis but not ROS-mediated tissue degeneration in SOD-deficient models.

show abstract

SOD1, more than just an antioxidant

Cited by 130 publications

References 179 publications

Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation

Dysregulations of Expression of Genes of the Ubiquitin/SUMO Pathways in an In Vitro Model of Amyotrophic Lateral Sclerosis Combining Oxidative Stress and SOD1 Gene Mutation

Transcriptional Changes after Enniatins A, A1, B and B1 Ingestion in Rat Stomach, Liver, Kidney and Lower Intestine

Pathological Relationship between Intracellular Superoxide Metabolism and p53 Signaling in Mice

Contact Info

Product

Resources

About