Among pro-inflammatory and other processes, progressive neuronal injury of the ischemic penumbra is associated with glutamate-induced depolarization, energetic stress and activation of AMP-activated protein kinase (AMPK), with the later triggering both pro-survival and pro-apoptotic signaling in neurons.
In summary, our observations demonstrate a role for the IFI16 protein in the energetic stress-induced activation of the ATM/AMPK/p53 pathway (Fig. 7) and autophagy.
It is known that environmental factors that place oxidative stress on cells promote the early onset of cellular senescence and increase the AMP: ATP ratio significantly (∼30-fold) [35], which results in energetic stress and activation of a stress pathway involving the AMPK and p53 [11].
During energetic stresses, the activation of AMPK limits protein synthesis and cell growth to protect against apoptosis through the TSC2/mTOR pathway.
Next, in MM.1S myeloma cell line the decrease in glucose consumption stimulated by purine analog 8-aminoadenosine application exerted energetic stress and activation of autophagy, which played role in cell redundancy to the treatment.
One important mechanism to maintain energetic homeostasis involves the activation of the energy sensor AMP-activated protein kinase (AMPK).
Therefore, our observations that glucose restriction (Fig. 1A) increases the activating phosphorylation of ATM protein kinase prompted us to test whether the activation of energetic stress in HDFs is the ATM-dependent.
Autophagy-induction in response to energetic stress is triggered by the activation of AMPK-activated protein kinase (AMPK 5, 6, a key, evolutionarily conserved energy sensor.
DNA damage induced by drugs, such as etoposide, also results in increased AMPK activity, via activation of ATM, as a mechanism to fulfill the energetic requirements of the DNA repair process.
To establish the link between the inflammatory response and the cellular energetic state, we assumed that upon activation of a pre-defined threshold the essential energetic response was assumed to subsequently modulate the degradation rate of TNF-a [38].
