The mtor inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration

Alia Albawardi, Saeeda Almarzooqi, Dhanya Saraswathiamma, Hidaya Mohammed Abdul-Kader, Abdul Kader Souid, Ali S. Alfazari

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)54-60
Number of pages7
JournalInternational Journal of Physiology, Pathophysiology and Pharmacology
Volume7
Issue number1
Publication statusPublished - 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)

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