Molecular Mechanism of T-2 Toxin-Induced Cerebral Edema by Aquaporin-4 Blocking and Permeation

• DOI: 10.1021/acs.jcim.9b00711
• Publication Date: 2019-10-23T19:03:19Z
• Authors: Nikhil Maroli; Naveen Kumar Kala...; Balu Bhasuran; Achuth Jayakrishnan; Renuka Ramalingam...; Ponmalai Kolandaivel; Jeyakumar Natarajan; Krishna Kadirvelu
• Keywords: Aquaporin 4

The present study aimed to reveal the molecular mechanism of T-2 toxin-induced cerebral edema by aquaporin-4 (AQP4) blocking and permeation. AQP4 is a class aquaporin channels that mainly expressed in brain, its structural changes lead life-threatening complications such as cardio-respiratory arrest, nephritis, irreversible brain damage. We employed dynamics simulation, text mining, vitro vivo analysis functional induced toxin on AQP4. action leads disrupted permeation water coefficients are found be affected, from native (2.49 ± 0.02 × 10-14 cm3/s) toxin-treated (7.68 0.15 channels. Furthermore, forms strong electrostatic interactions at binding site pushes key residues (Ala210, Phe77, Arg216, His201) outward selectivity filter. Also, role histidine residue channel was identified alchemical transformation umbrella sampling methods. Alchemical free-energy perturbation energy for H201A ↔ A201H, which 3.07 0.18 kJ/mol, indicates importance 201. In addition, histopathology expression Mus musculus tissues show damaged altered protein. Text mining reveals co-occurrence genes/proteins associated with cell apoptosis, edema.