Figure 1.
Nrf2 deficiency rescues redox homeostasis, prevents sudden cardiac death, and extends survival of the MPAC-TG mice. (A) Genotyping for human mutant R120GCryAB (TG) and Nrf2 deficiency (nrf2±) using specific primers sets. (B) Q-PCR determination of myocardial Nrf2-mRNA levels in NTG, MPAC-TG, and TG:Nrf2-def mice (n = 4–6/gp). (C) Immunoblots for the Nrf2 protein in the nuclear extracts of hearts from the above mouse models exhibiting either abundant (in MPAC-TG) or reduced Nrf2 (in TG:Nrf2-def) expression. (D) Immunoblots showing CryAB expression in the total homogenates of mouse hearts at 2 months of age. No significant difference was observed between TG vs. TG:Nrf2-def mice (n = 3/group). (E) Kaplan–Meier Survival plot (n ≥ 10 mice/group). (F) Representative images of hearts showing the gross morphology and reduced hypertrophy in Nrf2-def mice at 6–7 months of age. Images were obtained at 4× using a light microscope. (G) Heart-to-body weight ratios at 6–7 months of age showing significant hypertrophy in TG mice. (H) Quantitative PCR analysis of cardiac hypertrophy markers (n = 4–6/group). *NTG vs. TG; $NTG vs. TG:Nrf2-def; P < 0.05. (I) Myocardial GSH state determined by enzyme-kinetic assays (n = 4–6/group). (J) Scheme representing the transcriptional role of Nrf2 on antioxidants and GSH metabolism. *NTG vs. TG; $NTG vs. TG:Nrf2-def; P < 0.05.