Overexpression Bcl-2 alleviated ferroptosis induced by molybdenum and cadmium co-exposure through inhibiting mitochondrial ROS in duck kidneys

Abstract

Excessive molybdenum (Mo) and cadmium (Cd) are environmental pollutants with serious nephrotoxicity. B-cell lymphoma 2 (Bcl-2) plays a critical role in modulating mitochondrial ROS (Mito-ROS). Ferroptosis is a form of cell death dependent on lipid peroxidation. However, the impacts of Mo and Cd co-exposure on ferroptosis in duck kidneys and the function of Bcl-2 in the process are still unclear. Ducks and duck primary renal tubular epithelial cells exposed to different doses of Mo and/or Cd were used as the research target. Our work suggested that Mo and/or Cd significantly decreased Bcl-2 protein level and induced ferroptosis with the increase of ferrous ion, lipid peroxidation, TF protein level and the decrease of GPX4, FT protein levels. The Bcl-2 inhibitor HA14-1 exacerbated the changes of these indexes, but Bcl-2 overexpression had the opposite effect. Mito-ROS inhibitor ROS-IN-1 alleviated ferroptosis induced by Mo and Cd. Besides, Bcl-2 was involved in mitochondrial dysfunction induced by Mo and Cd, accompanied by disturbing Mito-ROS, ATP level, mitochondrial complex IV activity, Bcl-2 and COX-2 co-localization, lipid peroxidation, mitochondrial membrane potential (MMP) and mitochondrial structure. These findings substantiated that overexpression Bcl-2 alleviated ferroptosis co-induced by Mo and Cd through reducing Mito-ROS level in duck kidneys.

Keywords: Bcl-2; Cadmium; Ferroptosis; Mitochondrial ROS; Molybdenum.