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Mammalian target of rapamycin complex 2 regulates inflammatory response to stress

Desmond Mascarenhas1, Sheri Routt, Baljit K Singh

  • 1Mayflower Organization for Research and Education, 525 Del Rey Avenue, Suite B, Sunnyvale, CA 94085, USA. desmond@mayflowerworld.org

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|August 18, 2012
PubMed
Abstract

Insights

This study investigated the role of mammalian target of rapamycin 2 (mTORC2) in stress-induced inflammation and oxidative damage. Inhibiting mTORC2 with nephrilin reduced inflammatory markers and oxidative stress in rodent models.

Area of Science:

  • Biochemistry and Molecular Biology
  • Physiology
  • Toxicology

Background:

  • Mammalian target of rapamycin 2 (mTORC2) is a key signaling pathway involved in cellular growth and metabolism.
  • Inflammatory and oxidative responses are critical in acute injury and metabolic stress.

Purpose of the Study:

  • To investigate the role of mTORC2 in mediating inflammatory and oxidative responses in rodent models of acute injury and metabolic stress.
  • To assess the efficacy of nephrilin, an mTORC2 inhibitor, in mitigating these responses.

Main Methods:

  • Utilized CD-1 mouse models of acute xenobiotic stress and a hypertensive Dahl rat model of metabolic stress.
  • Administered daily subcutaneous injections of nephrilin or saline.
  • Analyzed tissue and plasma samples using ELISA, gene arrays, and immunohistochemical staining.

Main Results:

  • Nephrilin significantly reduced inflammatory markers (TNF-alpha, substance P, CX3CR1, uNGAL) in acute stress models.
  • In rhabdomyolysis, nephrilin reversed changes in UCHL1 and HMGB1.
  • In hypertensive rats, nephrilin inhibited diet-induced elevations in uNGAL, UACR, and key phosphorylation events (PKC-beta-2-T641, p66shc-S36).

Conclusions:

  • mTORC2 plays a significant role in the inflammatory and oxidative responses to acute injury and metabolic stress.
  • Inhibition of mTORC2 may represent a therapeutic strategy for managing stress-related conditions.

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