A possible speculation on the involvement of ROS and lysosomes mediated mitochondrial pathway in apoptosis of rotifer Brachionus plicatilis with BDE-47 exposure

Abstract

The toxicity and apoptosis induced by 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), one of the most widespread and bio-toxic brominated flame retardants (PBDEs) in marine ecosystem, were investigated and the possibly responsible mechanism was innovatively discussed from the perspective of mitochondrial pathway in marine rotifer Brachionus plicatilis. A series of BDE-47 exposure (0.08, 0,8 and 8 mg/L) led to the decrease of mitochondrial membrane potential (MMP) based on the strengthened fluorescence intensity, especially on stomach and ovary, which indicated the occurrence apoptosis. Further transmission electron microscopy (TEM) observation showed distinct ultrastructure impairment on mitochondria in the ovary. A pathway of mitochondria-ROS overproduction-apoptosis was thus speculated and proved. We first found that BDE-47 induced the increment of the ratio of pro-apoptosis protein Bax and anti-apoptosis protein Bcl-2 (Bax/Bcl-2), as well as the activities of key components caspase-9 and -3 in mitochondrial pathway in a clear concentration-dependent manner, accompanied by the simultaneous alteration of ROS production. The pretreatment of ROS inhibitor not only significantly attenuated ROS elevation but also decreased Bax/Bcl-2 ratio to some extent, and a strong positive correlation was found between ROS and Bax/Bcl-2 ratio. Interestingly, mitophagy was firstly observed in the damaged ultrastructure of B. plicatilis in 0.08 and 0.8 mg/L group, and the preliminary evidence of autophagosomes enabled the speculation of its involvement responding to BDE-47 stress. Taken together, we proposed that BDE-47 damaged the mitochondria that led to ROS overproduction, followed by the initiation of mitochondrial pathway. Speculatively, both apoptosis and mitophagy were assumed to involve in B. plicatilis coping with BDE-47 exposure.