Feng-Juan Li, Shouzhi Fu, Hua Ye, Yi-Han Hu, Jianxin Chen, Jamie R Privratsky, Wei Yu, Feng Dong, Russel J Reiter, Maolong Dong, Jun Guo, Jun Ren
This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. WT and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM in drinking water) for 14 days prior to assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity, intracellular Ca2+ handling, sarcoplasmic reticulum Ca2+ reuptake, loss of mitochondrial integrity (mitochondrial swelling, loss of aconitase activity), mitochondrial energy deficit, carbonyl damage, lipid peroxidation, ferroptosis and apoptosis...
February 26, 2024: American Journal of Pathology