p21

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.

p21

Postby admin » Fri May 22, 2020 8:50 pm

p21
© 2020 PFPC

p21 is also known as WAF1, CIP1, SDI1, and MDA-6. It is a cyclin kinase (CDK) inhibitor (Gartell et al., 1994).

p21 levels increase following the activation of p53 (Mansilla et al., 2020). In COVID-19, the lung damage observed is thought to be the result of apoptosis via P53 signalling pathway in lymphocytes (Xiong et al., 2020).

COVID-19

Re: chloroquine (CQ)

"In 2016, a Korean team found that the CQ up-regulates p21 (a CDK inhibitor) whose expression is suppressed by PAK1 [3,6]."


Maruta H, He H - "PAK1-blockers: Potential Therapeutics against COVID-19" Med Drug Discov 100039 (2020) doi: 10.1016/j.medidd.2020.100039. Epub ahead of print. PMID: 32313880; PMCID: PMC7166201.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166201/

Fluoride:

"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 H, Ikeda A, Cui H, Bartlett JD, Suzuki M - "MDM2-Mediated p21 Proteasomal Degradation Promotes Fluoride Toxicity in Ameloblasts" Cells 10;8(5):436 (2019) doi: 10.3390/cells8050436. PMID: 31083332; PMCID: PMC6562432.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562432/

"The results showed a positive relationship between fluoride exposure and expression of Cyclin d1/CDK4, and a negative relationship between fluoride exposure and expression of P21."


Pan X, Yan W, Qiu B, Liao Y, Liao Y, Wu S, Ming J, Zhang A - "Aberrant DNA methylation of Cyclind-CDK4-p21 is associated with chronic fluoride poisoning" Chem Biol Interact 315:108875 (2020) doi: 10.1016/j.cbi.2019.108875. Epub 2019 Oct 25. PMID: 31669217.
https://pubmed.ncbi.nlm.nih.gov/31669217/

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) doi: 10.1007/s00204-017-2135-2. Epub 2017 Nov 28. PMID: 29185024; PMCID: PMC6667832.

Gq/11

"In addition to its well known involvement in Gq/11-mediated vasoconstriction and its key roles in the homeostasis of electrolyte balances, the angiotensin II type 1 (AT1) receptor activates mitogen-activated protein kinase (MAPK) and p42/44 extracellular signal-regulated kinase. The extracellular signal-regulated kinase activation is mediated by activation of p21-Ras, Raf-1, and MAPK kinase in rat vascular smooth muscle cells.


Inagami T, Eguchi S, Numaguchi K, et al - "Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases" J Am Soc Nephrol 10 Suppl 11:S57‐S61 (1999)
https://pubmed.ncbi.nlm.nih.gov/9892141/

Coronavirus:
Lv X, Li Z, Guan J, et al. - "Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5β1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells" J Virol 93(5):e01736-18 (2019) Published 2019 Feb 19. doi:10.1128/JVI.01736-18
https://pubmed.ncbi.nlm.nih.gov/30541856/
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Gartel AL, Serfas MS, Tyner AL - "p21--negative regulator of the cell cycle" Proc Soc Exp Biol Med 213(2):138-49 (1996) doi: 10.3181/00379727-213-44046. PMID: 8931660
https://pubmed.ncbi.nlm.nih.gov/8931660/

Mansilla SF, de la Vega MB, Calzetta NL, Siri SO, Gottifredi V - "CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication" Genes (Basel). 2020 11(6):E593 (2020) doi: 10.3390/genes11060593. PMID: 32481484
https://pubmed.ncbi.nlm.nih.gov/32481484/
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