title: Endoplasmic Reticulum Stress Instigates the Rotenone Induced Oxidative Apoptotic Neuronal Death: a Study in Rat Brain.
abstract: The present study was conducted to evaluate the involvement of endoplasmic reticulum stress in rotenone-induced oxidative neuronal death in rat brain. Rotenone (6 μg/3 μl) was administered intranigrally, unilaterally (right side) in SD rat brain. Neuronal morphology, expression level of tyrosine hydroxylase (TH) and endoplasmic reticulum (ER) stress markers like glucose-regulated protein 78 (GRP78), growth arrest and DNA damage-inducible gene 153 (GADD153), eukaryotic translation initiation factor 2α (p-eIF2α/eIF2α) and cleaved caspase-12 were estimated in the rat brain. Levels of reactive oxygen species (ROS), reduced glutathione (GSH) and enzymatic activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) were estimated to assess the rotenone induced oxidative stress. Apoptotic death of neurons was assessed by estimating the mRNA level of caspase-3. Rotenone administration caused altered neuronal morphology, decreased expression of TH, augmented ROS level, decreased level of GSH and decreased activities of GPx and GRd enzymes which were significantly attenuated with the pretreatment of ER stress inhibitor, salubrinal (1 mg/kg, intraperitoneal). Significantly increased levels of GRP78, GADD, dephosphorylated eIF2α and cleaved caspase-12 was also observed after rotenone administration, which was inhibited with the pretreatment of salubrinal. Rotenone-induced increased mRNA level of caspase-3 was also attenuated by pretreatment of salubrinal. Findings suggested that salubrinal treatment significantly inhibited the rotenone-induced neurotoxicity implicating that ER stress initiates the rotenone-induced oxidative stress and neuronal death.
authors.affiliation: Toxicology Division, CSIR-CDRI, Lucknow, 226031, Uttar Pradesh, India.|Academy of Scientific and Innovative Research (AcSIR), Lucknow, 226031, Uttar Pradesh, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Goswami
authors.affiliation: Toxicology Division, CSIR-CDRI, Lucknow, 226031, Uttar Pradesh, India.
authors.forename: Sonam
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Toxicology Division, CSIR-CDRI, Lucknow, 226031, Uttar Pradesh, India.
authors.forename: Joyshree
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Toxicology Division, CSIR-CDRI, Lucknow, 226031, Uttar Pradesh, India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Toxicology Division, CSIR-CDRI, Lucknow, 226031, Uttar Pradesh, India. sarika_singh@cdri.res.in.|Academy of Scientific and Innovative Research (AcSIR), Lucknow, 226031, Uttar Pradesh, India. sarika_singh@cdri.res.in.
authors.forename: Sarika
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002934:Cinnamates; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C496827:salubrinal; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3; D005978:Glutathione; D013890:Thiourea
keywords: Apoptosis; Endoplasmic reticulum stress; Neurotoxicity; Oxidative stress; Rotenone; Salubrinal