Superoxide Dismutase 3 (SOD3)

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Superoxide Dismutase 3 (SOD3)

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Superoxide Dismutase 3 (SOD3)
© 2021 PFPC

Superoxide Dismutase is expressed as three distinct isoforms SOD1, SOD2, and SOD3. The SOD2 is in mitochondria, SOD3 is extracellular, and SOD1 is mainly found in cytoplasm (Fukai et al., 2011).

SOD3 is highly expressed in the extracellular matrix of the lung and plays a pivotal role against oxidative damage (Wei et al., 2017).

COVID-19

Superoxide dismutase 3 (SOD3) was identified as the top-ranked gene that was most downregulated in the lungs of the elderly in COVID-19 (Abouhashem et al., 2020).
  • Abouhashem AS, Singh K, Azzazy HME, Sen CK - "Is Low Alveolar Type II Cell SOD3 in the Lungs of Elderly Linked to the Observed Severity of COVID-19?" Antioxid Redox Signal 33(2):59-65 (2020) doi: 10.1089/ars.2020.8111. Epub 2020 May 8. PMID: 32323565; PMCID: PMC7307702
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307702/
  • SEE ALSO:

    Horowitz RI, Freeman PR, Bruzzese J - "Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases" Respir Med Case Rep 30:101063 (2020)
    https://pubmed.ncbi.nlm.nih.gov/32322478/

Fluoride

Animal studies have shown that fluoride has bi-phasic activities on SOD, in line with its firmly established reputation as a universal G-protein activator. At levels known to produce dental fluorosis in rodents, fluoride reduces SOD in lungs of rats (Aydin et al., 2003).
"The increased activities of superoxide dismutase (SOD) and reduced glutathione peroxidase (GSH-Px) and the decreased activity of catalase (CAT) in the lung tissues with 10 mg l(-1) fluoride might indicate activation of the antioxidant defence mechanism. The decrease in SOD, GSH-Px and CAT activities with 50 and 100 mg l(-1) fluoride and the increase in thiobarbituric acid-reactive substance levels might be related to oxidative damage that occurred in the lung." (Aydin et al., 2003) NOTE: Fluoride in water concentrations of 50 to 100 mg/L are required in rodents to produce similar effects as are observed in humans at much lower levels.
Aydin G, Ciçek E, Akdoğan M, Gökalp O - "Histopathological and biochemical changes in lung tissues of rats following administration of fluoride over several generations" J Appl Toxico 23(6):437-46 (2003). doi: 10.1002/jat.935. PMID: 14635268
https://pubmed.ncbi.nlm.nih.gov/14635268/

Mohammed AT, Mohamed AA, Ali H - "Pulmonary apoptotic and oxidative damaging effects of Triclosan alone or in combination with Fluoride in Sprague Dawley rats" Acta Histochem 119(4):357-363 (2017) doi: 10.1016/j.acthis.2017.03.004. Epub 2017 Apr 2. PMID: 28366506
https://pubmed.ncbi.nlm.nih.gov/28366506/
"The results of TCS or NaF treated groups revealed a prominent depletion of super oxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) in lung tissue homogenate." (Mohammed et al., 2017)

Ran LY, Xiang J, Zeng XX, Tang JL, Dong YT, Zhang F, Yu WF, Qi XL, Xiao Y, Zou J, Deng J, Guan ZZ - " Integrated transcriptomic and proteomic analysis indicated that neurotoxicity of rats with chronic fluorosis may be in mechanism involved in the changed cholinergic pathway and oxidative stress" J Trace Elem Med Biol 64:126688 (2021)
https://pubmed.ncbi.nlm.nih.gov/33260044/

Li Q, Zhang SH, Yu YH, Wang LP, Guan SW, Li PF - "Toxicity of sodium fluoride to Caenorhabditis elegans" Biomed Environ Sci 25(2):216-23 (2012) doi: 10.3967/0895-3988.2012.02.014. PMID: 22998830
https://pubmed.ncbi.nlm.nih.gov/22998830/

Alhusaini AM, Faddah LM, El Orabi NF, Hasan IH - "Role of Some Natural Antioxidants in the Modulation of Some Proteins Expressions against Sodium Fluoride-Induced Renal Injury" Biomed Res Int 2018:5614803 (2018)
https://pubmed.ncbi.nlm.nih.gov/30050936/


Gq/11

SOD is on the pathway activated by Gq/11 (i.e. see Greene et al., 2000).

Greene EL, Houghton O, Collinsworth G, Garnovskaya MN, Nagai T, Sajjad T, Bheemanathini V, Grewal JS, Paul RV, Raymond JR - " 5-HT(2A) receptors stimulate mitogen-activated protein kinase via H(2)O(2) generation in rat renal mesangial cells" Am J Physiol Renal Physiol 278(4):F650-8 (2000)
https://pubmed.ncbi.nlm.nih.gov/10751227/
receptor --> G(q) protein --> phospholipase C --> diacylglycerol [DAG] --> classical PKC --> NAD(P)H oxidase --> superoxide --> superoxide dismutase [SOD] --> H(2)O(2) --> mitogen-activated extracellular signal-regulated kinase [MAPK] --> ERK.

Descorbeth M, Anand-Srivastava MB - "Role of oxidative stress in high-glucose- and diabetes-induced increased expression of Gq/11α proteins and associated signaling in vascular smooth muscle cells" Free Radic Biol Med 49(9):1395-405 (2010) doi: 10.1016/j.freeradbiomed.2010.07.023. Epub 2010 Aug 5. PMID: 20691780


Thyroid

Roseni Mundstock Dias G, Medeiros Golombieski R, de Lima Portella R, Pires do Amaral G, Antunes Soares F, Teixeira da Rocha JB, Wayne Nogueira C, Vargas Barbosa N - "Diphenyl diselenide modulates gene expression of antioxidant enzymes in the cerebral cortex, hippocampus and striatum of female hypothyroid rats" Neuroendocrinology 100(1):45-59 (2014)
https://pubmed.ncbi.nlm.nih.gov/25012258/
"Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3)...The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain."


TSH

Laatikainen LE, Castellone MD, Hebrant A, Hoste C, Cantisani MC, Laurila JP, Salvatore G, Salerno P, Basolo F, Näsman J, Dumont JE, Santoro M, Laukkanen MO - "Extracellular superoxide dismutase is a thyroid differentiation marker down-regulated in cancer" Endocr Relat Cancer 17(3):785-96 (2010)
https://pubmed.ncbi.nlm.nih.gov/20576801/
"We showed TSH-stimulated expression of Sod3 via phospholipase C-Ca(2+) and cAMP-protein kinase A, a pathway that might be disrupted in thyroid cancer."

Peixoto MS, de Vasconcelos E Souza A, Andrade IS, de Carvalho El Giusbi C, Coelho Faria C, Hecht F, Miranda-Alves L, Ferreira ACF, Carvalho DP, Fortunato RS - "Hypothyroidism induces oxidative stress and DNA damage in breast" Endocr Relat Cancer 28(7):505-519 (2021)
https://pubmed.ncbi.nlm.nih.gov/34010147/

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https://pubmed.ncbi.nlm.nih.gov/?term=SOD+TSH&sort=date
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