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Indian Journal of Dental Research :... 2022Oral leukoplakia has recently been re-defined as "a predominantly white lesion of the oral mucosa that cannot be characterised as any other definable lesion". Superoxide...
CONTEXT AND AIM
Oral leukoplakia has recently been re-defined as "a predominantly white lesion of the oral mucosa that cannot be characterised as any other definable lesion". Superoxide dismutase (SOD) is one of the enzymatic anti-oxidants which form the first line of defence in the cell. There are very limited data available on the analysis of SOD in leukoplakia patients. Therefore, the present study was planned to analyse anti-oxidant SOD levels in leukoplakia patients.
METHODS AND MATERIAL
The study group consisted of 29 subjects of oral leukoplakia, and the control group consisted of 25 healthy individuals. All the subjects were evaluated for SOD enzyme in plasma.
STATISTICAL ANALYSIS USED
The results for each determinant were calculated using one-way ANOVA test, Student 't' test, Pearson Chi square test, and 't' test for equality of means wherever applicable.
RESULTS
The study revealed that among the different clinical entities of oral leukoplakia, the enzymatic anti-oxidant SOD is shown to have decreased in all forms of oral leukoplakia, but without any statistical significance. A statistically highly significant decrease (at P < 0.0001) of SOD in oral leukoplakia patients compared to normal healthy patients was observed in the present study.
CONCLUSIONS
The study revealed a difference in the free-radical activity and oxidative stress in blood of leukoplakia patients compared to healthy patients, which is reflected by the variation in the levels of blood SOD, thus showing vulnerability to cellular damage and tendency towards further malignant changes.
Topics: Humans; Antioxidants; Leukoplakia, Oral; Superoxide Dismutase; Oxidative Stress; Mouth Mucosa
PubMed: 36656190
DOI: 10.4103/ijdr.ijdr_1009_21 -
Signal Transduction and Targeted Therapy Dec 2023Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to...
Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1 mice and ALS patients. SOD1 mice treated with primidone showed significant delay of symptomatic onset and improved motor performance. One-hundred-sixty-two ALS participants dosed daily with primidone (62.5 mg) completed 24-week follow-up. A significant reduction was showed in serum levels of RIPK1 and IL-8, which were significantly higher in ALS patients than that of healthy controls (P < 0.0001). Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms (P < 0.05). Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients. Repurposing primidone may provide a promising therapeutic strategy for ALS. The effect of primidone for the treatment of other inflammatory diseases may also be considered, since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome (CRS). (ChiCTR2200060149).
Topics: Animals; Humans; Mice; Amyotrophic Lateral Sclerosis; Biomarkers; Interleukin-8; Mice, Transgenic; Motor Neurons; Neurodegenerative Diseases; Primidone; Protein Kinases; Receptor-Interacting Protein Serine-Threonine Kinases; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 38086800
DOI: 10.1038/s41392-023-01713-z -
Adipocyte Jan 2017Reactive oxygen species (ROS) production and oxidative stress (OS) in adipose tissue are associated with obesity and insulin resistance (IR). The nature of this... (Review)
Review
Reactive oxygen species (ROS) production and oxidative stress (OS) in adipose tissue are associated with obesity and insulin resistance (IR). The nature of this relationship i.e., cause and effect or consequence has not been clearly determined. We provide evidence that elevated mitochondrial ROS generated by adipocytes from mice with diet-induced obesity (DIO) represents an adaptive mechanism that precipitates fatty acid oxidation, mitochondrial biogenesis, and mitochondrial uncoupling in an effort to defend against weight gain. Consistent with that, mice with adipocyte-specific deletion of manganese superoxide dismutase (MnSOD) exhibit increased adipocyte superoxide generation and are protected from weight gain and insulin resistance which otherwise develops in wild-type (WT) mice that consume an obesogenic diet. The defense mechanism displayed by MnSOD-deficiency in fat cells appears to be mediated by a dual effect of ROS on inefficient substrate oxidation through uncoupling of oxidative phosphorylation and enhanced mitochondrial biogenesis. The aim of this commentary is to summarize and contextualize additional evidence supporting the importance of mitochondrial ROS in the regulation of mitochondrial biogenesis and the modulation of uncoupling protein 1 (UCP1) expression and activation in both white and brown adipocytes.
Topics: Adipocytes; Animals; Energy Metabolism; Mice; Mitochondria; Mitochondrial Proteins; Organelle Biogenesis; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase; Uncoupling Protein 1
PubMed: 28452586
DOI: 10.1080/21623945.2016.1273298 -
Redox Biology Feb 2024Oxidative stress (OS) is regarded as the dominant theory for aging. While compelling correlative data have been generated to support the OS theory, a direct...
Oxidative stress (OS) is regarded as the dominant theory for aging. While compelling correlative data have been generated to support the OS theory, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and aging has not been firmly established. Superoxide dismutase 1 (SOD1) is a primary antioxidant in all cells. It is, however, susceptible to oxidation due to OS and gains toxic properties to cells. This study investigates the role of oxidized SOD1 derived from amyotrophic lateral sclerosis (ALS) linked SOD1 mutations in cell senescence and aging. Herein, we have shown that the cell line NSC34 expressing the G93A mutation of human SOD1 (hSOD1) entered premature senescence as evidenced by a decreased number of the 5-ethynyl-2'-deoxyuridine (EdU)-positive cells. There was an upregulation of cellular senescence markers compared to cells expressing the wild-type human SOD1 (hSOD1). Transgenic mice carrying the hSOD1 gene showed aging phenotypes at an early age (135 days) with high levels of P53 and P16 but low levels of SIRT1 and SIRT6 compared with age-matched hSOD1 transgenic mice. Notably, the levels of oxidized SOD1 were significantly elevated in both the senescent NSC34 cells and 135-day hSOD1 mice. Selective removal of oxidized SOD1 by our CT4-directed autophagy significantly decelerated aging, indicating that oxidized SOD1 is a causal factor of aging. Intriguingly, mitochondria malfunctioned in both senescent NSC34 cells and middle-aged hSOD transgenic mice. They exhibited increased production of mitochondrial-derived vesicles (MDVs) in response to mild OS in mutant humanSOD1 (hSOD1) transgenic mice at a younger age; however, the mitochondrial response gradually declined with aging. In conclusion, our data show that oxidized SOD1 derived from ALS-linked SOD1 mutants is a causal factor for cellular senescence and aging. Compromised mitochondrial responsiveness to OS may serve as an indicator of premature aging.
Topics: Animals; Humans; Infant; Mice; Middle Aged; Aging; Amyotrophic Lateral Sclerosis; Disease Models, Animal; Mice, Transgenic; Motor Neurons; Mutation; Sirtuins; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 38056310
DOI: 10.1016/j.redox.2023.102972 -
PloS One 2021Oxidative stress, which could be evoked by numerous inducements including mycotoxins like deoxynivalenol (DON), cause severe damages to organisms. Antioxidants are...
Oxidative stress, which could be evoked by numerous inducements including mycotoxins like deoxynivalenol (DON), cause severe damages to organisms. Antioxidants are promising protectants against oxidative stress that could be applied in pharmaceutical, cosmetic, and food and feed industries. In this study, a thermostable and acidophilic superoxide dismutase (AaSOD) was used to develop an antioxidant product that can potentially protect organisms from oxidative stress related damages. The enzyme was successfully expressed as an extracelluar protein in Bacillus subtilis with a high yield. To obtain a feasible protocol for industrial production of AaSOD, the fermentation mediums that are commonly used for culturing B. subtilis were screened, the feasibility of expressing AaSOD without antibiotic as selection pressure was confirmed, and the effect of using lactose as an inducer instead of isopropyl-β-d-thiogalactoside (IPTG) was investigated. Batch fermentation was conducted to validate the optimized conditions for AaSOD production, and 6530 U mL-1 of SOD activity was obtained in the fermentation broth. The dry powder product of AaSOD with an activity of 22202 U g-1 was prepared by spray-drying and was administrated on zebrafish to test its function as a protectant against DON, and thus gained a significant redress of the reactive oxygen species (ROS) accumulation induced by DON. Taken together, this study provides a feasible protocol to prepare the AaSOD-based antioxidant product that is potentially applied in livestock industry.
Topics: Animals; Bacillus subtilis; Bacterial Proteins; Batch Cell Culture Techniques; Cloning, Molecular; Culture Media; Enzyme Stability; Fermentation; Mycotoxins; Oxidative Stress; Protein Engineering; Reactive Oxygen Species; Superoxide Dismutase; Thermodynamics; Zebrafish
PubMed: 34784394
DOI: 10.1371/journal.pone.0260047 -
Scientific Reports Oct 2023Global warming is a critical challenge limiting crop productivity. Heat stress during cucumber growing stages caused deterioration impacts on the flowering, fruit, and...
Global warming is a critical challenge limiting crop productivity. Heat stress during cucumber growing stages caused deterioration impacts on the flowering, fruit, and yield stages. In this study, "inbred line 1 and hybrid P1 × P2" (heat-tolerant) and "Barracuda" (heat-sensitive) were utilized to determine the heat tolerance in summer season. The heat injury index was used to exhibit the heat tolerance performance. The heat injury index for heat tolerant (HT) genotypes, on leaves (HIIL%) and female flowers (HIIF%), was less than 25 and 15 % in HT, compared to heat sensitive (HS) was more than 75 and 85%, respectively. Moreover, the content of leaf chlorophyll, proline, brassinosteroid (BRs), abscisic acid content (ABA), the activity of catalase (CAT, EC 1.11. 1.6), peroxidase (POD, EC 1.11.1.7) and superoxide dismutase (SOD, EC 1.15.1.1) increased with the heat stress responses in HT plants. Expression pattern analyses of eight genes, related to POD (CSGY4G005180 and CSGY6G015230), SOD (CSGY4G010750 and CSGY1G026400), CAT (CsGy4G025230 and CsGy4G025240), and BR (CsGy6G029150 and CsGy6G004930) showed a significant increase in HT higher than in HS plants. This study furnishes valuable markers for heat tolerance genotypes breeding in cucumber and provides a basis for understanding heat-tolerance mechanisms.
Topics: Cucumis sativus; Thermotolerance; Plant Breeding; Superoxide Dismutase; Heat-Shock Response
PubMed: 37907590
DOI: 10.1038/s41598-023-45163-7 -
The Journal of Biological Chemistry Mar 2018This 11th Thematic Metals in Biology Thematic Series deals with copper, a transition metal with a prominent role in biochemistry. Copper is a very versatile element, and... (Review)
Review
This 11th Thematic Metals in Biology Thematic Series deals with copper, a transition metal with a prominent role in biochemistry. Copper is a very versatile element, and both deficiencies and excesses can be problematic. The five Minireviews in this series deal with several aspects of copper homeostasis in microorganisms and mammals and the role of this metal in two enzymes, copper-only superoxide dismutase and cytochrome oxidase.
Topics: Animals; Copper; Electron Transport Complex IV; Humans; Superoxide Dismutase
PubMed: 29425098
DOI: 10.1074/jbc.TM118.002255 -
International Journal of Molecular... Apr 2023Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are...
Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression system carried on the vector, motor neurons were efficiently and rapidly generated from iPSCs by a single-step induction method. Induced iPSC transcripts displayed characteristics similar to those of spinal cord neurons. iPSC-generated motor neurons carried a mutation in () and () genes and had abnormal protein accumulation corresponding to each mutation. Calcium imaging and multiple electrode array (MEA) recordings demonstrated that ALS neurons were abnormally hyperexcitable. Noticeably, protein accumulation and hyperexcitability were ameliorated by treatment with rapamycin (mTOR inhibitor) and retigabine (Kv7 channel activator), respectively. Furthermore, rapamycin suppressed ALS neuronal death and hyperexcitability, suggesting that protein aggregate clearance through the activation of autophagy effectively normalized activity and improved neuronal survival. Our culture system reproduced several ALS phenotypes, including protein accumulation, hyperexcitability, and neuronal death. This rapid and robust phenotypic screening system will likely facilitate the discovery of novel ALS therapeutics and stratified and personalized medicine for sporadic motor neuron diseases.
Topics: Humans; Amyotrophic Lateral Sclerosis; Induced Pluripotent Stem Cells; Motor Neurons; Superoxide Dismutase-1; Mutation; Phenotype; Superoxide Dismutase
PubMed: 37108151
DOI: 10.3390/ijms24086987 -
Yakugaku Zasshi : Journal of the... 2019Excessive generation of reactive oxygen species (ROS) has been implicated in the progression of tumors. Superoxide dismutase 3 (SOD3) is a copper-containing secretory... (Review)
Review
Excessive generation of reactive oxygen species (ROS) has been implicated in the progression of tumors. Superoxide dismutase 3 (SOD3) is a copper-containing secretory antioxidative enzyme that plays a critical role in redox homeostasis, particularly in extracellular spaces. Considerable evidence suggests that SOD3 protein expression is significantly decreased or lost in several tumor tissues, and this loss results in tumor metastasis. On the other hand, epigenetic disturbances, including DNA hyper-/hypomethylation, histone de/acetylation, and histone de/methylation, may be involved in tumorigenesis and the progression of metastasis. However, regulation of SOD3 in the tumor microenvironment and the involvement of epigenetics in its expression remain unclear. To elucidate the molecular mechanisms underlying SOD3 expression, we investigated the involvement of epigenetics, including DNA methylation and histone modifications, in its regulation in tumor cells and macrophages. SOD3 expression in human monocytic THP-1 cells and human lung cancer A549 cells was silenced by DNA hypermethylation within the SOD3 promoter region. Furthermore, the DNA demethylase, ten-eleven translocation 1, was shown for the first time to play a key role in regulation of DNA methylation within that region. We also demonstrated that myocyte enhancer factor 2 functioned as one of the transcription factors of SOD3 expression in THP-1 cells. Collectively, these novel results will contribute to the elucidation of epigenetic redox regulation, and may provide important insights into tumorigenesis and tumor metastasis.
Topics: Carcinogenesis; DNA Methylation; Disease Progression; Epigenesis, Genetic; Gene Expression; Histone Code; Homeostasis; Humans; Neoplasm Metastasis; Neoplasms; Oxidation-Reduction; Reactive Oxygen Species; Superoxide Dismutase; Tumor Microenvironment
PubMed: 31474628
DOI: 10.1248/yakushi.19-00128 -
Acta Neuropathologica Jan 2023Mutations in the gene encoding the ubiquitously expressed free radical scavenging enzyme superoxide dismutase-1 (SOD1) are found in 2-6% of amyotrophic lateral sclerosis...
Mutations in the gene encoding the ubiquitously expressed free radical scavenging enzyme superoxide dismutase-1 (SOD1) are found in 2-6% of amyotrophic lateral sclerosis patients. The most frequent SOD1 mutation worldwide is D90A. Amyotrophic lateral sclerosis caused by this mutation has some unusual features: the heredity is usually recessive, the phenotype is stereotypic with slowly evolving motor symptoms beginning in the legs and may also include sensory, autonomic, and urinary bladder involvement. Furthermore, the mutant protein resembles the wild type, with normal content and enzymatic activity in the central nervous system. Here, we report neuropathological findings in nine patients homozygous for the D90A mutation. All nine had numerous small granular inclusions immunoreactive for misfolded SOD1 in motor neurons and glial nuclei in the spinal cord and brainstem. In addition to degeneration of the corticospinal tracts, all patients had degeneration of the dorsal columns. We also found intense gliosis in circumscribed cortical areas of the frontal and temporal lobes and in the insula. In these areas and in adjacent white matter, there were SOD1 staining neuropil threads. A few SOD1-immunopositive cytoplasmic neuronal inclusions were observed in cortical areas, as were glial nuclear inclusions. As suggested by the symptoms and signs and earlier neurophysiological and imaging investigations, the histopathology in patients homozygous for the D90A SOD1 extends beyond the motor system to include cognitive and sensory cortical areas. However, even in the patients that had a symptomatic disease duration of more than 2 or 3 decades and lived into their 70s or 80s, there were no SOD1-inclusion pathology and no typical dysfunction (apart from the musculature) in non-nervous organs. Thus, only specific parts of the CNS seem to be vulnerable to toxicity provoked by homozygously expressed mutant SOD1.
Topics: Humans; Amyotrophic Lateral Sclerosis; Superoxide Dismutase-1; Superoxide Dismutase; Central Nervous System; Motor Neurons; Mutation; Pyramidal Tracts
PubMed: 36385230
DOI: 10.1007/s00401-022-02519-z