Anastrozole-mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: an initial perspective
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Anastrozole, MD simulation, binding sites, docking complexes, mitochondrial disorders, mitochondrial permeability transition pore, molecular docking, protein targets, structural modelling,
- MeSH
- Adenosine Triphosphate metabolism MeSH
- Anastrozole pharmacology metabolism MeSH
- Cyclophilins genetics metabolism MeSH
- Leukocytes, Mononuclear metabolism MeSH
- Humans MeSH
- Mitochondrial Diseases * metabolism MeSH
- Mitochondria metabolism MeSH
- Peptidyl-Prolyl Isomerase F MeSH
- Mitochondrial Permeability Transition Pore * metabolism pharmacology MeSH
- Mitochondrial Membrane Transport Proteins metabolism pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adenosine Triphosphate MeSH
- Anastrozole MeSH
- Cyclophilins MeSH
- Peptidyl-Prolyl Isomerase F MeSH
- Mitochondrial Permeability Transition Pore * MeSH
- Mitochondrial Membrane Transport Proteins MeSH
The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole-CypD complex is more stable than cyclosporin A (CsA)-CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings.Communicated by Ramaswamy H. Sarma.
Amrita School of Biotechnology Amrita University Clappana PO Kerala India
Department of Biomedical Sciences Acharya Narendra Dev College University of Delhi Delhi India
Department of Emergency Medicine All India Institute of Medical Sciences New Delhi India
Department of Microbiology World College of Medical Science and Research Jhajjar Haryana India
Department of Zoology Kirori Mal College University of Delhi Delhi India
Institute of Nuclear Medicine and Allied Sciences Delhi India
Molecular Oncology Laboratory Department of Zoology University of Delhi Delhi India
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