Eur Rev Med Pharmacol Sci 2022; 26 (1): 168-182

DOI: 10.26355/eurrev_202201_27766

Organophosphates modulate tissue transglutaminase activity in differentiated C6 neural cells

M.A. Aldubayan, I.S. Almami, S.G. Felemban, A.H. Alhowail, P.L.R. Bonner, A.J. Hargreaves

School of Science and Technology, Nottingham Trent University, Nottingham, UK. m.aldubayan@qu.edu.sa


OBJECTIVE: The organophosphate compounds chlorpyrifos (O, O-diethyl O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate, CPF) and phenyl saligenin phosphate (PSP) have been widely implicated in developmental neurotoxicity and neurodegeneration. However, the underlying mechanism remains unclear. Transglutaminase (TG)2 is a calcium ion (Ca2+)-dependent enzyme with an important role in neuronal cell outgrowth and differentiation and in neurotoxin activity and is modulated by organophosphates.

MATERIALS AND METHODS: We studied TG2 activity modulation by CPO and PSP during differentiation in C6 glioma cells. We studied the effects of CPO or PSP treatment with or without the TG2 inhibitor Z-DON and identified potential TG2 protein substrates via mass spectrometry.

RESULTS: PSP and CPO did not affect cell viability but affected TG2 activity in differentiating cells. Our results indicate that the organophosphate-induced amine incorporation activity of TG2 may have a direct effect on neuronal outgrowth, differentiation, and cell survival by modifying several essential microtubule proteins, including tubulin. Inhibiting TG2 reduced neurite length but not cell survival.

CONCLUSIONS: TG2 inhibitors can protect against organophosphate-induced neuropathy and could be used for developing novel therapeutic strategies for treating brain cancer and neurodegenerative disorders.

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M.A. Aldubayan, I.S. Almami, S.G. Felemban, A.H. Alhowail, P.L.R. Bonner, A.J. Hargreaves
Organophosphates modulate tissue transglutaminase activity in differentiated C6 neural cells

Eur Rev Med Pharmacol Sci
Year: 2022
Vol. 26 - N. 1
Pages: 168-182
DOI: 10.26355/eurrev_202201_27766