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• W2624041622 endingPage "185" @default.
• W2624041622 startingPage "175" @default.
• W2624041622 abstract "Activation of PI3K/Akt signaling, leading to upregulation of nitric oxide synthase II (NOS II)/peroxynitrite cascade in the rostral ventrolateral medulla (RVLM), the brain stem site that maintains blood pressure and sympathetic vasomotor tone, underpins cardiovascular depression induced by the organophosphate pesticide mevinphos. By exhibiting dual-specificity protein- and lipid-phosphatase activity, phosphatase and tensin homolog (PTEN) directly antagonizes the PI3K/Akt signaling by dephosphorylation of phosphatidylinositol-3,4,5-trisphosphate, the lipid product of PI3K. Based on the guiding hypothesis that PTEN may sustain brain stem cardiovascular regulation during mevinphos intoxication as a negative regulator of PI3K/Akt signaling in the RVLM, we aimed in this study to clarify the mechanistic role of PTEN in mevinphos-induced circulatory depression. Microinjection bilaterally of mevinphos (10 nmol) into the RVLM of anesthetized Sprague-Dawley rats induced a progressive hypotension and a decrease in baroreflex-mediated sympathetic vasomotor tone. There was progressive augmentation in PTEN activity as reflected by a decrease in the oxidized form of PTEN in the RVLM during mevinhpos intoxication, without significant changes in the mRNA or protein level of PTEN. Loss-of-function manipulations of PTEN in the RVLM by immunoneutralization, pharmacological blockade or siRNA pretreatment significantly potentiated the increase in Akt activity or NOS II/peroxynitrite cascade in the RVLM, enhanced the elicited hypotension and exacerbated the already reduced baroreflex-mediated sympathetic vasomotor tone. We conclude that augmented PTEN activity via a decrease of its oxidized form in the RVLM sustains brain stem cardiovascular regulation during mevinphos intoxication via downregulation of the NOS II/peroxynitrite cascade as a negative regulator of PI3K/Akt signaling." @default.
• W2624041622 created "2017-06-15" @default.
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• W2624041622 date "2017-09-01" @default.
• W2624041622 modified "2023-10-16" @default.
• W2624041622 title "PTEN, a negative regulator of PI3K/Akt signaling, sustains brain stem cardiovascular regulation during mevinphos intoxication" @default.
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• W2624041622 doi "https://doi.org/10.1016/j.neuropharm.2017.06.007" @default.
• W2624041622 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28601397" @default.
• W2624041622 hasPublicationYear "2017" @default.
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