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Published on: October 23, 2018
Nutrient withdrawal rescues growth factor-deprived cells from mTOR-dependent damage
Emiliano Panieri1, Gabriele Toietta, Marina Mele
1Institute of General Pathology, Laboratory of Cell Signaling, Catholic University Medical School, Rome Italy.
Aging
|August 27, 2010
Summary
Nutrient signaling impacts aging and diabetes. Inhibiting the mTOR/S6K pathway protects cells from nutrient excess and growth factor scarcity, offering new therapeutic targets for age-related diseases and diabetes.
Area of Science:
- Cellular and Molecular Biology
- Metabolic Signaling
- Aging Research
Background:
- Deregulated nutrient signaling is implicated in aging and diabetic complications.
- The precise biochemical pathways linking energy imbalance to cell damage are not fully understood.
- Novel molecular targets are needed to address these conditions.
Purpose of the Study:
- To investigate the role of nutrient metabolism and signaling pathways in cell survival and death.
- To identify molecular targets for mitigating cell damage associated with nutrient dysregulation.
- To explore the involvement of the mTOR/S6K pathway in nutrient-induced cell damage.
Main Methods:
- Utilized HEK293-T Phoenix cell line and human umbilical vein endothelial cells (HUVEC).
- Manipulated nutrient availability (glucose, amino acids) and employed inhibitors (2-deoxy-glucose).
- Assessed mitochondrial function, oxidative stress, and signaling pathways (mTOR/S6K, AMPK, Sirt-1).
- Used pharmacological and genetic approaches to modulate pathway activity.
Main Results:
- Nutrient withdrawal and glycolysis inhibition protected cells from death in serum-free conditions.
- mTOR/S6K cascade activity was reduced by nutrient restriction.
- Modulation of the mTOR pathway inversely affected S6K/S6 signaling and cell viability.
- AMP-activated Protein Kinase stimulation inhibited mTOR signaling and cell death.
- mTOR blockade reduced hyperglycemic damage in HUVECs.
Conclusions:
- The mTOR/S6K cascade plays a critical role in cellular damage induced by nutrient excess and growth factor scarcity.
- This pathway is a potential therapeutic target for conditions like diabetes and aging-related pathologies.
- Energy metabolism and specific signaling cascades are key determinants of cell survival under nutrient stress.
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