Low O2 and high CO2 in LLC-PK1 cells culture mimics renal ischemia-induced apoptosis.

Ischemia, absence or loss of blood flow in organs always presents as a dual phenomenon: tissue oxygen deficit and CO(2) excess (hypercapnia). Commonly hypoxic cell culture models kept CO(2) at normal nonischemic values. We report a study of apoptosis in an in vitro model of renal hypoxia that mimics in vivo tissue gas atmosphere composition determined during experimental ischemia in rat kidney (low O(2) plus high CO(2)). Renal tubular LLC-PK1 cell were transiently exposed to hypoxia, to hypercapnia or to both conditions (simulated ischemia). Exposure to simulated ischemic atmosphere, but not to low O(2) or high CO(2) alone, induced cell apoptosis in vitro. This suggests that ischemia-induced apoptosis in vivo would be dependent on the natural, joint action of hypoxia and hypercapnia. This should be taken into account in cell culture studies that would like to mimic in vivo ischemic conditions.