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Cell hydration and mTOR-dependent signalling.

F Schliess1, L Richter, S vom Dahl

  • 1Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University, Düsseldorf, and San Francisco Hospital, Department for Internal Medicine, Cologne, Germany. schliess@med.uni-duesseldorf.de

Acta Physiologica (Oxford, England)
|June 1, 2006
PubMed
Summary

Cell hydration impacts mammalian target of rapamycin (mTOR) signaling. While swelling may activate mTOR, its inhibition is not always linked to proteolysis, suggesting complex roles in cell metabolism and insulin resistance.

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[Not Available].

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Area of Science:

  • Cellular Biology
  • Metabolic Signaling
  • Physiology

Background:

  • Mammalian target of rapamycin (mTOR) signaling, crucial for protein metabolism, is activated by insulin and amino acids.
  • mTOR signaling involves p70 ribosomal S6 protein kinase (p70S6-kinase) and eukaryotic initiation factor 4E (eIF4E) binding protein 4E-BP1 hyperphosphorylation.

Purpose of the Study:

  • To review the impact of cell hydration status on mTOR-dependent signaling pathways.
  • To explore the relationship between cell volume changes and mTOR signaling in regulating protein metabolism and cellular functions.

Main Methods:

  • Review of existing literature on mTOR signaling and cell hydration.
  • Analysis of studies investigating mTOR activity under hypo-osmotic and hyper-osmotic conditions in various cell types (hepatocytes, adipocytes).

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Main Results:

  • Hypoosmotic swelling can activate p70S6-kinase, but proteolysis inhibition in rat liver is rapamycin-insensitive.
  • Insulin- and leucine-induced proteolysis inhibition in rat liver is also rapamycin-insensitive, indicating mTOR independence.
  • Hyperosmotic dehydration inactivates mTOR signaling components, impairing insulin-stimulated glucose uptake, glycogen synthesis, and lipogenesis in adipocytes.

Conclusions:

  • Rapamycin-sensitive mTOR signaling is not universally involved in hydration-induced changes in protein metabolism.
  • Cell dehydration can directly impair mTOR signaling, affecting key metabolic processes.
  • Understanding the interplay between cell hydration and mTOR signaling is vital for comprehending health and disease, particularly insulin resistance.