Anastrozole-mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: an initial perspective
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- Klíčová slova
- Anastrozole, MD simulation, binding sites, docking complexes, mitochondrial disorders, mitochondrial permeability transition pore, molecular docking, protein targets, structural modelling,
- MeSH
- adenosintrifosfát metabolismus MeSH
- anastrozol farmakologie metabolismus MeSH
- cyklofiliny genetika metabolismus MeSH
- leukocyty mononukleární metabolismus MeSH
- lidé MeSH
- mitochondriální nemoci * metabolismus MeSH
- mitochondrie metabolismus MeSH
- peptidylprolylisomerasa F MeSH
- přechodový pór mitochondriální permeability * metabolismus farmakologie MeSH
- transportní proteiny mitochondriální membrány metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfát MeSH
- anastrozol MeSH
- cyklofiliny MeSH
- peptidylprolylisomerasa F MeSH
- přechodový pór mitochondriální permeability * MeSH
- transportní proteiny mitochondriální membrány 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
Citace poskytuje Crossref.org
