A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Activation of apoptosis and P53 signalling pathway in lymphocytes
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"SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia". (Xiong et al., 2020)
Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A, Guo D, Hu W, Yang J, Tang Z, Wu H, Lin Y, Zhang M, Zhang Q, Shi M, Liu Y, Zhou Y, Lan K, Chen Y - "Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients" Emerg Microbes Infect 9(1):761-770 (2020). doi: 10.1080/22221751.2020.1747363. PMID: 32228226; PMCID: PMC7170362

"Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers." (Wen et al., 2019)

Wen P, Wei X, Liang G, Wang Y, Yang Y, Qin L, Pang W, Qin G, Li H, Jiang Y, Wu Q - "Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers." Environ Sci Pollut Res Int 26(3):2671-2680 (2019). doi: 10.1007/s11356-018-3726-z. Epub 2018 Nov 26. PMID: 30478774
https://link.springer.com/article/10.10 ... 018-3726-z
"Fluoride overexposure is an environmental health hazard and can cause enamel and skeletal fluorosis. Previously we demonstrated that fluoride increased acetylated-p53 and its downstream target p21 in ameloblast-derived LS8 cells.... Inhibition of MDM2-mediated p21 degradation may be a potential therapeutic target to mitigate fluoride toxicity." (Deng et al., 2019)

Deng H, Ikeda A, Cui H, Bartlett JD, Suzuki M - "MDM2-Mediated p21 Proteasomal Degradation Promotes Fluoride Toxicity in Ameloblasts" Cells 8(5):436 (2019) doi: 10.3390/cells8050436. PMID: 31083332; PMCID: PMC6562432.
"The SIRT1/p53 pathway may be a potential therapeutic target for dental fluorosis."(Suzuki et al., 2017)
Suzuki M, Ikeda A, Bartlett JD - " Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation" Arch Toxicol 92(3):1283-1293 (2018)
https://www.ncbi.nlm.nih.gov/pmc/articl ... 67832/#R27

Qing-Feng S, Ying-Peng X, Tian-Tong X - "Matrix metalloproteinase-9 and p53 involved in chronic fluorosis induced blood-brain barrier damage and neurocyte changes" Arch Med Sci 15(2):457-466 (2019) doi: 10.5114/aoms.2019.83294. Epub 2019 Mar 4. PMID: 30899299; PMCID: PMC6425220

Xiang J, Qi XL, Cao K, Ran LY, Zeng XX, Xiao X, Liao W, He WW, Hong W, He Y, Guan ZZ - "Exposure to fluoride exacerbates the cognitive deficit of diabetic patients living in areas with endemic fluorosis, as well as of rats with type 2 diabetes induced by streptozotocin via a mechanism that may involve excessive activation of the poly(ADP ribose) polymerase-1/P53 pathway" Sci Total Environ 169512 (2023). doi: 10.1016/j.scitotenv.2023.169512. Epub ahead of print

How is Gq/11 involved?
"Immune responses are coordinated by the extracellular ligand to GPCR on lymphocytes, and activated intracellular Gq protein then activates enzymes, second messengers, protein kinases, and nuclear translocation, consequently inducing the migration, activation, and apoptosis of lymphocytes [48]. This well-orchestrated function of hematopoietic cells is complex; however, it is clear that Gq-coupled receptors and the signaling molecules that reside downstream of these receptors are critical to these functions." (Zhang & Shi, 2016; Molon et al, 2005)

Molon B, Gri G, Bettella M, Gómez-Moutón C, Lanzavecchia A, Martínez-A C, Mañes S, Viola A - "T cell costimulation by chemokine receptors" Nat Immunol 6(5):465-71 (2005)

Zhang Lu, Shi Guixiu - "Gq-Coupled Receptors in Autoimmunity" Journal of Immunology Research (2016)

p53 and thyroid hormones

Zou M, Baitei EY, Al-Rijjal RA, Parhar RS, Al-Mohanna FA, Kimura S, Pritchard C, Binessa HA, Alzahrani AS, Al-Khalaf HH, Hawwari A, Akhtar M, Assiri AM, Meyer BF, Shi Y - "TSH overcomes Braf(V600E)-induced senescence to promote tumor progression via downregulation of p53 expression in papillary thyroid cancer" Oncogene 35(15):1909-18 (2016) doi: 10.1038/onc.2015.253. Epub 2015 Oct 19. PMID: 26477313; PMCID: PMC6310059.

Xian H, Wang F, Teng W, Yang D, Zhang M - "Thyroid hormone induce a p53-dependent DNA damage through PI3K/Akt activation in sperm" Gene 615:1-7 (2017) doi: 10.1016/j.gene.2017.03.014. Epub 2017 Mar 16. PMID: 28322991.
Buckbinder L, Velasco-Miguel S, Chen Y, Xu N, Talbott R, Gelbert L, Gao J, Seizinger BR, Gutkind JS, Kley N - "The p53 tumor suppressor targets a novel regulator of G protein signaling" Proc Natl Acad Sci U S A 94(15):7868-72 (1997) doi: 10.1073/pnas.94.15.7868. PMID: 9223279; PMCID: PMC21521.

SEE ALSO: p21. viewtopic.php?f=66&t=1928
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