Open AccessTat‐antioxidant 1 protects against stress‐induced hippocampal HT ‐22 cells death and attenuate ischaemic insult in animal model
Author(s) -
Kim So Mi,
Hwang In Koo,
Yoo Dae Young,
Eum Won Sik,
Kim Dae Won,
Shin Min Jea,
Ahn Eun Hee,
Jo Hyo Sang,
Ryu Eun Ji,
Yong Ji In,
Cho SungWoo,
Kwon OhShin,
Lee Keun Wook,
Cho Yoon Shin,
Han Kyu Hyung,
Park Jinseu,
Choi Soo Young
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12513
Subject(s) - oxidative stress , microbiology and biotechnology , reactive oxygen species , programmed cell death , mapk/erk pathway , chemistry , lipid peroxidation , biology , signal transduction , apoptosis , biochemistry
Oxidative stress‐induced reactive oxygen species ( ROS ) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS . The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat‐Atox1 and examined the roles of Tat‐Atox1 in oxidative stress‐induced hippocampal HT ‐22 cell death and an ischaemic injury animal model. Tat‐Atox1 effectively transduced into HT ‐22 cells and it protected cells against the effects of hydrogen peroxide (H 2 O 2 )‐induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat‐Atox1 regulated cellular survival signalling such as p53, Bad/Bcl‐2, Akt and mitogen‐activate protein kinases ( MAPK s). In the animal ischaemia model, transduced Tat‐Atox1 protected against neuronal cell death in the hippocampal CA 1 region. In addition, Tat‐Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA 1 region after ischaemic insult. Taken together, these results indicate that transduced Tat‐Atox1 protects against oxidative stress‐induced HT ‐22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat‐Atox1 has potential as a therapeutic agent for the treatment of oxidative stress‐induced ischaemic damage.