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

Ching Yi Tsai*, Kuang Yu Dai, Chi Fang, Jacqueline C.C. Wu, Samuel H.H. Chan

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

11 Scopus citations


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 counteracted by PTEN, a negative regulator of PI3K/Akt signaling. The concept that a classical signaling pathway in tumorigenesis is also an active player in cardiovascular dysregulation in brain stem death provides new ramifications for translational medicine. It promulgates the concept that rather than focusing on a particular disease condition, a new vista for future therapeutic strategy against both fatal eventualities should target at this common cellular cascade.

Original languageEnglish
Pages (from-to)207-212
Number of pages6
JournalBiochemical Pharmacology
StatePublished - 09 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Elsevier Inc.


  • Experimental brain stem death
  • FLJ10540
  • PI3K/Akt
  • PTEN
  • Rostral ventrolateral medulla


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