August 2019
Volume 60Issue 8p1347-1490
Open Access
COVER: The lipid mediator lysophosphatidic acid (LPA) and the lysophospholipase D enzyme
(autotaxin), which generates LPA, are integral components of the cellular response
triggered by genotoxic stress. Genotoxic stress synergistically activates the DNA
damage response and a radiation-induced surge of cytokines that converge on the Akt-NFkB
pathway. In turn, NFkB mediates the transcriptional upregulation of the LPA2 GPCR
and autotaxin, which are responsible for long-lasting activation prosurvival, DNA
repair, and anti-apoptotic signals. LPA2-specific agonists offer therapeutic potential
as radiation mitigative drug candidates. (See Tigyi et al. in the JLR March issue, p. 464.)...Show more
COVER: The lipid mediator lysophosphatidic acid (LPA) and the lysophospholipase D enzyme
(autotaxin), which generates LPA, are integral components of the cellular response
triggered by genotoxic stress. Genotoxic stress synergistically activates the DNA
damage response and a radiation-induced surge of cytokines that converge on the Akt-NFkB
pathway. In turn, NFkB mediates the transcriptional upregulation of the LPA2 GPCR
and autotaxin, which are responsible for long-lasting activation prosurvival, DNA
repair, and anti-apoptotic signals. LPA2-specific agonists offer therapeutic potential
as radiation mitigative drug candidates. (See Tigyi et al. in the JLR March issue, p. 464.)
