mitochondrial complex i is an essential player in lps-induced preconditioning in differentiated pc12 cells

Preconditioning (pc) as a protective strategy against noxious insults can decline cell death and apoptosis. it has been approved that mitochondria play a key role in pc mechanism. the critical role of complex i (ci) in oxidative phosphorylation machinery and intracellular ros production, particularly in the brain, accentuates its possible role in pcinduced neuroprotection. here, differentiated pc12 cells were preconditioned with ultralow dose lps (uld, 3 μg/ml) prior to exposure to high concentration of lps (hd, 750 μg/ml). our results showed that hd lps treatment reduces cell viability and ci activity, and intensifies expression of cleaved caspase 3 compared to the control group. intriguingly, pc induction resulted in enhancement of cell 2 viability and ci activity and reduction of caspase 3 cleavage compared to hd lps group. in order to explore the role of ci in pc, we combined the uld lps with rotenone, a ci inhibitor. following rotenone administration, cell viability significantly reduced while caspase 3 cleavage increased compared to pc induction group. taken together, cell survival and reduction of apoptosis followed by pc can be at least partially attributed to the preservation of mitochondrial ci function.