The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines

Abstract

The mitochondrial translocator protein (TSPO) is a modulator of the apoptotic pathway involving reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) collapse, activation of caspases, and eventually initiation of the apoptotic process. In this in vitro study, H1299 lung cells and BV-2 microglial cells were exposed to the hypoxia-like effect of CoCl2 with or without PK 11195. Exposing the H1299 cells to 0.5 mM CoCl2 for 24 h resulted in decreases in cell viability (63%, p p p p 2-induced alterations in the mentioned processes. Exposure of BV-2 cells to increasing concentrations of CoCl2 (0.3, 0.5, 0.7 mM) for 4 h resulted in alterations in the same cellular processes. These alterations were obtained in a dose-dependent manner, except the changes in caspases 3 and 9. The novel ligands as well as PK 1195 attenuated the in vitro hypoxia-like effects of CoCl2. It appears that the TSPO ligand PK 11195 can prevent CoCl2-induced cellular damage in both non-neuronal and brain cell lines, and they may offer a novel approach to the treatment of hypoxia-related lung and brain diseases in some cases that fail to respond to conventional therapies.

Keywords

• hypoxia-like condition
• H1299
• BV-2
• CoCl₂
• PK 11195