RT Journal Article
SR Electronic
T1 Anastrozole mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: An initial perspective
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 724872
DO 10.1101/724872
A1 Somesh Kumar
A1 Subhajit Ghosh
A1 Neha Choudhary
A1 Mohammed Faruq
A1 Prem kumar Inderganti
A1 Vikram Singh
A1 Ravindra kumar Saran
A1 Haseena Sait
A1 Seema Kapoor
YR 2019
UL http://biorxiv.org/content/early/2019/08/05/724872.abstract
AB Background Mitochondrial permeability transmembrane pore [mPTP] plays a vital role in alteration of the structure and function of mitochondria. Cyclophillin D is a mitochondrial protein that regulates mPTP function and a known drug target for therapeutic studies involving mitochondria. While aromatase inhibitor’s role on mPTP has been previously studied, the role of anastrazole on mPTP is not completely elucidated.Methods The role of anastrozole in modulating the mPTP was evaluated by docking and molecular dynamics using human cyclophillin D data. Peripheral blood mononuclear cells [PBMCs] of patients with mitochondrial disorders and healthy controls were treated with anastrazole and evaluated for mean fluorescence by flow cytometer. Spectrophotometry was employed for total ATP level estimation.Findings Anastrozole – cyclophillin D complex is more stable when compared to cyclosporine A – cyclophillin D. Anastrozole performed better than cyclosporine in inhibiting mPTP pore. Additional effects included reduction in mitochondrial swelling and mitochondrial membrane depolarization, decreased super oxide generations, caspase 3 intrinsic activity and cellular apoptosis levels and increase in ATP levels.Interpretation These results highlights the potency of anastrozole as a promising agent in ameliorating the phenotype by inhibiting the opening of mPTP pore. However, larger functional studies are required to validate the efficacy of this molecule as a therapeutic agent in mitochondrial disorders.