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http://dx.doi.org/10.5487/TR.2018.34.3.267

Proteomic Changes in Chick Brain Proteome Post Treatment with Lathyrus Sativus Neurotoxin, β-N-Oxalyl-L-α,β-Diaminopropionic Acid (L-ODAP): A Better Insight to Transient Neurolathyrism  

Anil Kumar, D (Department of Biochemistry, University College of Science, Osmania University)
Natarajan, Sumathi (Department of Biochemistry, University College of Science, Osmania University)
Omar, Nabil A M Bin (Department of Biochemistry, University College of Science, Osmania University)
Singh, Preeti (Bharati Vidyapeeth Medical College)
Bhimani, Rohan (Hinduja Healthcare, Khar West)
Singh, Surya Satyanarayana (Department of Biochemistry, University College of Science, Osmania University)
Publication Information
Toxicological Research / v.34, no.3, 2018 , pp. 267-279 More about this Journal
Abstract
Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.
Keywords
L-ODAP; Neurolathyrism; Chick brain proteome; Mitochondria membrane potential; Caspase; Apoptosis;
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