Relation of excess calcium accumulation to calcium-dependent apoptotic cell death in RCR-1 cells exposed to tributyltin

抄録

In this study, we examined the effect of tributyltin chloride (TBTC) on astrocytes that act as a blood-brain barrier. After exposure to 1 µM TBTC, RCR-1 cells (a rat astrocytoma cell line) induced apoptosis, such as caspase-3 activation and DNA fragmentation. TBTC exposure also induced excessive increases in intracellular calcium in RCR-1 cells, at which time calcium from cytosol was remarkably transferred to the nuclei. TBTC-induced apoptosis was suppressed when RCR- 1 cells were incubated in Dulbecco's Phosphate-Buffered Saline (DPBS) buffer without calcium, or were pretreated with BAPTA-AM (1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester), an intracellular calcium chelator. Furthermore, significant activation of calpain was associated with calcium-dependent enzyme action and an increase of intracellular calcium was confirmed in TBTC-exposed RCR-1 cells. On the other hand, calpain activation was suppressed in the absence of both extracellular and intracellular calcium. These results indicate the presence of a TBTC-induced calcium-dependent apoptotic pathway in RCR-1 cells. In conclusion, the current results suggest that increased TBTC transfer to brain tissue, such as with various brain disorders is due to the loss of blood-brain barrier (BBB) permeability caused by TBTC-induced apoptosis in astrocytes.