PTEN/FLJ10540/PI3K/Akt cascade in experimental brain stem death: A newfound role for a classical tumorigenic signaling pathway

Biochemical Pharmacology
Ching-Yi TsaiSamuel H H Chan

Abstract

Despite great advances in contemporary medicine, brain death still remains enigmatic and its cellular and molecular mechanisms unsettled. This review summarizes recent findings that substantiate the notion that PTEN/FLJ10540/PI3K/Akt cascade, the classical tumorigenic signaling pathway, is actively engaged in experimental brain stem death. These results were based on a clinically relevant animal model that employs the pesticide mevinphos as the experimental insult in Sprague-Dawley rats to mimic brain stem death in patients died of organophosphate poisoning. The neural substrate investigated is the rostral ventrolateral medulla (RVLM), a brain stem site classically known to maintain arterial pressure (AP) and is established to be the origin of a "life-and-death" signal detected from AP, which reflects brain stem cardiovascular dysregulation that precedes death. Activation of PI3K/Akt signaling pathway in the RVLM upregulates the nuclear factor-κB/nitric oxide synthase II/peroxynitrite cascade, resulting in impairment of brain stem cardiovascular regulation that leads to the loss of the "life-and-death" signal in experimental brain stem death. This process is reinforced by FLJ10540, a PI3K-association protein; and is counteracte...Continue Reading

Citations

Mar 17, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Hardeep Singh TuliKatrin Sak
Aug 28, 2020·Brain Research Bulletin·Li Zhang, Handong Wang

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