{Reference Type}: Journal Article {Title}: Exogenous sulfide regulates hypoxia/reoxygenation stress through the intrinsic apoptotic pathway in the blood clam (Tegillarca granosa). {Author}: Wang Y;Xia F;Jia S;Yang Y;Zhang X; {Journal}: Comp Biochem Physiol C Toxicol Pharmacol {Volume}: 283 {Issue}: 0 {Year}: 2024 Sep 8 {Factor}: 4.52 {DOI}: 10.1016/j.cbpc.2024.109953 {Abstract}: The intertidal organism Tegillarca granosa can survive under frequent hypoxia/reoxygenation (H/R) exposure. Sulfides as accompanying products in benthic hypoxic environments, may play an important regulatory role, but the mechanisms are not well understood. This article investigated the physiological and molecular changes of T. granosa after adding different concentrations of sulfides (0.1, 0.5, 1 mM) at 72 h into a 120-h exposure to hypoxia, as well as the recovery state of 24 h of reoxygenation. The results indicated that H/R stress induces ROS production and mild mitochondrial depolarization in clams, and sulfide can participate in its regulation. Among them, a low concentration of sulfide up-regulated glutathione content and alternative oxidase activity, maintained the stability of antioxidant enzymes, and up-regulated the expression of the survival genes XIAP/BCL-xl which mediate cell survival via the NFκB signaling pathway. High concentrations of sulfide had a significant inhibitory effect on the p38/MPAK pathway and inhibited intrinsic apoptosis caused by ROS accumulation during reoxygenation. Taken together, our study suggested that different concentrations of sulfides are involved in regulating the endogenous apoptosis of clams during H/R.