The Effect of the Classical TSPO Ligand PK 11195 On in Vitro Cobalt Chloride Model of Hypoxia in Non-Neuronal and Brain Cell Lines

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 hypoxic effect of CoCl2 with or without PK 11195. Exposing the H1299 cells to 0.5 mM CoCl2 for 24 hours resulted in decreases in cell viability (63%, p<0.05), elevation of cardiolipin peroxidation levels (38%, p<0.05), mitochondrial membrane potential depolarization (13%, p<0.001), and apoptotic cell death (117%, p<0.05). Pretreatment with PK 11195 (25 µM) exhibited significant protective capacity on CoCl2-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 hours 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 hypoxic 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 new therapeutic options in hypoxia-related lung and brain diseases which fail to respond to conventional therapies.

Neuroligin affects metastatic performance of CD66+ cells: Theoretical analysis of Multi-tissue RNA expressions through System modeling based Network mapping under in-vitro constraints

ABSTRACTPresent study deals with theoretical analysis of multi-tissue RNA expressions through system model based network mapping under the constraints of in-vitro experiments. Here, effect of Neuroligin was evaluated on the performance of metastatic behavior of CD66+ cells of human female reproductive cell lines. Total 10 genes and 14 cell lines were considered in the study. Clustering of cell lines was done on the basis of network mapping under the same homeostatic constraints. Neuroligin was found to affect metastatic performance of CD66+ cells. Two CD66+ cell lines hTERT-HME1 and SK-BR-3 were found to most effective, in similar manner as brain cell lines as U-138MG & U-87MG.