Abstract
The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus - rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, p = 0.002), hepatic (39%, p < 0.001), and cardiac (42%, p = 0.005) cellular respiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.
Original language | English |
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Pages (from-to) | 54-60 |
Number of pages | 7 |
Journal | International Journal of Physiology, Pathophysiology and Pharmacology |
Volume | 7 |
Issue number | 1 |
Publication status | Published - Jan 1 2015 |
Keywords
- Cyclosporine
- MTOR
- O<inf>2</inf> consumption
- Oxidative phosphorylation
- Rapamycin
- Sirolimus
- Tacrolimus
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Physiology
- Physiology (medical)