SVCT2, a potential therapeutic target, protects against oxidative stress during ethanol-induced neurotoxicity via JNK/p38 MAPKs, NF-κB and miRNA125a-5p.

SVCT2, a potential therapeutic target, protects against oxidative stress during ethanol-induced neurotoxicity via JNK/p38 MAPKs, NF-κB and miRNA125a-5p.
Free Radic Biol Med. 2016 Apr 13;
Authors: Tian H, Ye X, Hou X, Yang X, Yang J, Wu C
Abstract
Sodium vitamin C transporter 2 (SVCT2) plays a key role in transporting ascorbic acid (AA), an important intracellular antioxidant, into neurons. It is well known that ethanol (EtOH) abuse causes significant neurodegeneration, as well as endogenous AA release in certain encephalic regions. Here, we identified that SVCT2 forms part of a self-defense mechanism that protects against oxidative stress in binge drinking rats, and SVCT2 levels are correlated with antioxidants and neuronal injury. Four days of binge drinking led to massive neuron degeneration in prefrontal cortex (PFC), accompanied by increased levels of 4-hydroxynonenal (4-HNE)-adducted proteins and SVCT2 expression, as well as dramatic changes in AA levels in rat brain. AA levels were decreased in PFC and increased in CSF after binge drinking, but returned to normal on the 7(th) day following EtOH withdrawal. These processes were further evaluated in primary cortical neurons exposed to 100mM EtOH in vitro. Neurons transfected with SVCT2 siRNA were more susceptible than controls to certain aspects of EtOH-induced injury, including cell death, dendrite damage and increased oxidative stress. EtOH-induced up-regulation of SVCT2 was a...

Source: Free Radical Biology and Medicine - April 12, 2016 Category: Biology Authors: Tian H, Ye X, Hou X, Yang X, Yang J, Wu C Tags: Free Radic Biol Med Source Type: research