LKB1/AMPK/M-TOR response to ischemia in high metabolic rate tissues: A comparison between the brain, heart, kidney and liver intracellular metabolic axis activation in ischemic situation

The cellular energy depletion due to ischaemia is one of the most stressful situations for the cells, in particularly for those with a high metabolic rate. To protect the cells against the consequence of a metabolic disturbed situation, the energy sensing Liver Kinase B1 (LKB1)/Adenosine Monophosphate Kinase Protein Kinase (AMPK) pathway regulates the cellular balance of energy. Here we studied the activation of LKB1/AMPK axis along with their down-steam regulatory kinase, Mammalian target of rapamycin (mTOR) in response to a time-dependent ischaemic situation (15 sec to 8 min) in the brain, heart, kidney and liver using a rat model of reversible cardiac arrest (CA). Our results demonstrated that LKB1 phosphorylation decreased in the brain after 30 sec ischaemia, while it increased after 4 min in the heart and kidney, and remained unchanged in the liver. AMPK activity increased in the brain after 8 min following a significant decrease in the shorter periods of ischaemia, decreased in up to 1 min ischaemia in the kidney and showed an increase in the heart after 8 min of ischaemia. m-TOR phosphorylation didn’t show any alteration in the heart, kidney and liver, while it increased after 4 and 8 min of ischaemia. We concluded that LKB1/AMPK/m-TOR axis acts in different ways in response to the same duration of ischemia, such as a less phosphorylation level of the first sensors in a tissue with less glucose resources (brain) as an early response, but the same or the higher phosphorylation levels for the tissues with some glucose resources such as the liver, kidney or the heart.