Boerma 2015 Radiat Res
| Boerma M, Singh P, Sridharan V, Tripathi P, Sharma S, Singh SP (2015) Effects of local heart irradiation in a glutathione S-transferase alpha 4-null mouse model. Radiat Res 183:610-9. |
Boerma M, Singh P, Sridharan V, Tripathi P, Sharma S, Singh SP (2015) Radiat Res
Abstract: Glutathione S-transferase alpha 4 (GSTA4-4) is one of the enzymes responsible for the removal of 4-hydroxynonenal (4-HNE), an electrophilic product of lipid peroxidation in cellular membranes during oxidative stress. 4-HNE is a direct activator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a transcription factor with many target genes encoding antioxidant and anti-electrophile enzymes. We have previously shown that Gsta4-null mice on a 129/Sv background exhibited increased activity of Nrf2 in the heart. Here we examined the sensitivity of this Gsta4-null mouse model towards cardiac function and structure loss due to local heart irradiation. Male Gsta4-null and wild-type mice were exposed to a single X-ray dose of 18 Gy to the heart. Six months after irradiation, immunohistochemical staining for respiratory complexes 2 and 5 indicated that radiation exposure had caused most pronounced alterations in mitochondrial morphology in Gsta4-null mice. On the other hand, wild-type mice showed a decline in cardiac function and an increase in plasma levels of troponin-I, while no such changes were observed in Gsta4-null mice. Radiation-induced Nrf2-target gene expression only in Gsta4-null mice. In conclusion, although loss of GSTA4-4 led to enhanced susceptibility of cardiac mitochondria to radiation-induced loss of morphology, cardiac function was preserved in Gsta4-null mice. We propose that this protection against cardiac function loss may occur, at least in part, by upregulation of the Nrf2 pathway.
Labels: MiParea: Respiration
Organism: Mouse
Tissue;cell: Heart
Preparation: Permeabilized tissue
Coupling state: OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
