Protection from oxidative and electrophilic stress in the Gsta4-null mouse heart.
Protection from oxidative and electrophilic stress in the Gsta4-null mouse heart.
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DOI：
10.1007/s12012-013-9215-1
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发表时间：
2013-12
影响因子：
3.2
通讯作者：
Singh SP
中科院分区：
文献类型：
--
作者：
Beneš H;Vuong MK;Boerma M;McElhanon KE;Siegel ER;Singh SP
4-hydroxynonenal (4-HNE) mediates many pathological effects of oxidative and electrophilic stress and signals to activate cytoprotective gene expression regulated by NF-E2-related factor 2 (Nrf2). By exhibiting very high levels of 4-HNE-conjugating activity, the murine glutathione transferase alpha 4 (GSTA4-4) helps regulate cellular 4-HNE levels. To examine the role of 4-HNE in vivo, we disrupted the murine Gsta4 gene. Gsta4-null mice exhibited no cardiac phenotype under normal conditions and no difference in cardiac 4-HNE level as compared to wild-type (WT) mice. We hypothesized that the Nrf2 pathway might contribute an important compensatory mechanism to remove excess cardiac 4-HNE in Gsta4-null mice. Cardiac nuclear extracts from Gsta4-null mice exhibited significantly higher Nrf2 binding to antioxidant-response elements (AREs). We also observed responses in critical Nrf2 target gene products: elevated Sod2, Cat, and Akr1b7 mRNA levels and significant increases in both cardiac anti-oxidant and anti-electrophile enzyme activities. Gsta4-null mice were less sensitive and maintained normal cardiac function following chronic doxorubicin (DOX) treatment, known to increase cardiac 4-HNE levels. Hence, in the absence of GSTA4-4 to modulate both physiological and pathological 4-HNE levels, the adaptive Nrf2 pathway may be primed to contribute to a preconditioned cardiac phenotype in the Gsta4-null mouse.
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影响因子：
20.1
作者：
Dai DF;Rabinovitch PS;Ungvari Z
通讯作者：
Ungvari Z
DOI：
10.1253/circj.cj-08-1082
发表时间：
2009-02
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Heistad DD;Wakisaka Y;Miller J;Chu Y;Pena-Silva R
通讯作者：
Pena-Silva R
影响因子：
15.9
作者：
DOROSHOW, JH;LOCKER, GY;MYERS, CE
通讯作者：
MYERS, CE
影响因子：
5
作者：
Churchill, Eric N.;Disatnik, Marie-Helene;Mochly-Rosen, Daria
通讯作者：
Mochly-Rosen, Daria
影响因子：
3.2
作者：
Desmots, F;Rissel, M;Guillouzo, A
通讯作者：
Guillouzo, A