Alteration in cytoskeletal protein levels in sciatic nerve on post-treatment of diisopropyl phosphorofluoridate (DFP)-treated hen with phenylmethylsulfonyl fluoride

Abstract

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, and a single dose (1.7 mg/kg, sc.) of this compound produces mild ataxia in hens in 7-14 days and a severe ataxia or paralysis (OPIDN) in three weeks. OPIDN is associated with axonal swelling and their degeneration. We have previously observed alteration in neurofilament (NF) protein levels in the spinal cord of DFP-treated hens. The main objective of this investigation was to study NF protein levels in the sciatic nerves (SN) of hens, in which OPIDN has been potentiated by phenylmethylsulfonyl fluoride (PMSF) post-treatment. PMSF is known to protect DFP-treated (1.7 mg/kg) hens from developing OPIDN if injected before, and potentiate OPIDN if injected after the administration of DFP (0.5 mg/kg). The potentiation of OPIDN was accompanied by earlier elevation of NF proteins in the SN particulate fraction. In contrast, SN supernatant fraction showed a transient fall in NF protein levels in potentiation OPIDN. Out of the two other cytoskeletal proteins (i.e., tubulin, tau) studied in this investigation, tubulin also showed earlier elevation in its level in the particulate fraction in potentiated OPIDN. The earlier elevation of NF protein levels in SN particulate fraction in potentiated OPIDN suggested the possible involvement of NFs in delayed neurotoxicity.