NFE2L2 and ischemia: In this respect, earlier evidence has suggested that H2S can induce NRF2 nuclear accumulation and protect cardiomyocytes against ischemia [123], while later studies showed that H2S could inactivate KEAP1 by promoting the formation of an intramolecular disulfide bond (C226–C613) and thereby induce NRF2 stabilization, at least in part through H2O2 generation.