Diacylglycerol (DAG)

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

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Diacylglycerol (DAG)
©2020 PFPC

DAG is the downstream effector of the activated Gq/11 signaling pathway (phosphoinositol pathway).

COVID-19

"Plasma lipidome of COVID-19 resembled that of monosialodihexosyl ganglioside (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs)." (Song et al., 2020)


Song JW, Lam SM, Fan X, Cao WJ, Wang SY, Tian H, Chua GH, Zhang C, Meng FP, Xu Z, Fu JL, Huang L, Xia P, Yang T, Zhang S, Li B, Jiang TJ, Wang R, Wang Z, Shi M, Zhang JY, Wang FS, Shui G - "Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis" Cell Metab 32(2):188-202.e5 (2020) doi: 10.1016/j.cmet.2020.06.016. Epub 2020 Jun 24. PMID: 32610096; PMCID: PMC7311890
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311890/

Yuan S, Yan B, Cao J, Ye ZW, Liang R, Tang K, Luo C, Cai J, Chu H, Chung TW, To KK, Hung IF, Jin DY, Chan JF, Yuen KY - "SARS-CoV-2 exploits host DGAT and ADRP for efficient replication" Cell Discov 7(1):100 (2021)
https://pubmed.ncbi.nlm.nih.gov/34702802/

Fluoride

"In addition, production of cellular diacylglycerol (DAG) was significantly increased in fluorosed ameloblasts, suggesting that the increased phosphorylation of SATB1 may be related to an effect of fluoride to enhance Gαq activity of secretory ameloblasts."(Zhang et al., 2014)


Zhang Y, Kim JY, Horst O, Nakano Y, Zhu L, Radlanski RJ, Ho S, Den Besten PK - "Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity" PLoS One 9(8):e103994 (2014) doi: 10.1371/journal.pone.0103994. PMID: 25090413; PMCID: PMC4121220
https://pubmed.ncbi.nlm.nih.gov/25090413/

Olson SC, Tyagi SR, Lambeth JD - "Fluoride activates diradylglycerol and superoxide generation in human neutrophils via PLD/PA phosphohydrolase-dependent and -independent pathways" FEBS Lett 272(1-2):19-24 (1990) doi: 10.1016/0014-5793(90)80439-p. PMID: 2172014
https://pubmed.ncbi.nlm.nih.gov/2172014/

Nambi P, Aiyar N, Wu HL, Crooke ST - "Possible involvement of protein kinase C and cyclic AMP-dependent protein kinase in the sodium fluoride-mediated inhibition of cyclic nucleotide accumulation in smooth muscle cells" Cell Signal 2(6):531-6 (1990) doi: 10.1016/0898-6568(90)90075-l. PMID: 2081095.
https://pubmed.ncbi.nlm.nih.gov/2081095/

Gq/11

"AT1B receptors are coupled to Gq/11 (Guanine protein coupled receptor, or GPCR); they increase phospholipase beta C (PLC) activity resulting in inositol 1,4,5 triphosphate (InsP3) and diacylglycerol (DAG) formation. A biphasic increase in [Ca2+]i triggered by InsP3 and DAG ensues."(Suárez et al., 2002)


Suárez C, Tornadú IG, Cristina C, Vela J, Iglesias AG, Libertun C, Díaz-Torga G, Becu-Villalobos D - "Angiotensin and calcium signaling in the pituitary and hypothalamus" Cell Mol Neurobio 22(3):315-33 (2002) doi: 10.1023/a:1020772018703. PMID: 12469873.
https://pubmed.ncbi.nlm.nih.gov/12469873/

Zhang Y, Kim JY, Horst O, Nakano Y, Zhu L, Radlanski RJ, Ho S, Den Besten PK - "Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity" PLoS One 9(8):e103994 (2014) doi: 10.1371/journal.pone.0103994. PMID: 25090413; PMCID: PMC4121220
https://pubmed.ncbi.nlm.nih.gov/25090413/

Thyroid

"These findings suggest that DAG that is produced from cellular PC through PC-PLC plays an essential role in the TSH-induced PKC/PLD activation."(Kim et al., 2009)


Kim JH, Kim SW, Jung PJ, Yon C, Kim SC, Han JS - "Phosphatidylcholine-specific phospholipase C and RhoA are involved in the thyrotropin-induced activation of phospholipase D in FRTL-5 thyroid cells" Mol Cells 14(2):272-80 (2002) PMID: 12442901
http://www.molcells.org/journal/view.ht ... &spage=272

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PFAS

Schillemans T, Shi L, Donat-Vargas C, Hanhineva K, Tornevi A, Johansson I, Koponen J, Kiviranta H, Rolandsson O, Bergdahl IA, Landberg R, Åkesson A, Brunius C - "Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study" Environ Int 146:106180 (2021)
"The diacylglycerols also correlated positively with PFAS..."

SEE: PFAS
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