ArticleInternational journal of physiology, pathophysiology and pharmacology2015
The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.
Article in International journal of physiology, pathophysiology and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
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Who cites it
7 citing papers in PubMed.
- Effect of Sirolimus/Metformin Co-Treatment on Hyperglycemia and Cellular Respiration in BALB/c Mice.International journal of molecular sciences · 2023Article
- Sirolimus treatment induces dose-dependent involution of the thymus with elevated cellular respiration in BALB/c mice.American journal of translational research · 2022Article
- Cardiovascular effects of immunosuppression agents.Frontiers in cardiovascular medicine · 2022Review
- Glucocorticoid-dependent REDD1 expression reduces muscle metabolism to enable adaptation under energetic stress.BMC biology · 2018Article
- Sirolimus alters lung pathology and viral load following influenza A virus infection.Respiratory research · 2017Article
- The PI3Kδ inhibitor idelalisib suppresses liver and lung cellular respiration.International journal of physiology, pathophysiology and pharmacology · 2015Article
- Effects of molecularly targeted therapies on murine thymus: highly selective mTOR inhibitors induce reversible thymic involution.Experimental hematology & oncology · 2015Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
Indexed as
Identifiers
26069529PMC4446389What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.