title: Effects of 4-phenyl butyric acid on high glucose-induced alterations in dorsal root ganglion neurons.
abstract: Mechanisms and pathways involving in diabetic neuropathy are still not fully understood but can be unified by the process of overproduction of reactive oxygen species (ROS) such as superoxide, endoplasmic reticulum (ER) stress, downstream intracellular signaling pathways and their modulation. Susceptibility of dorsal root ganglion (DRG) to internal/external hyperglycemic environment stress contributes to the pathogenesis and progression of diabetic neuropathy. ER stress leads to abnormal ion channel function, gene expression, transcriptional regulation, metabolism and protein folding. 4-phenyl butyric acid (4-PBA) is a potent and selective chemical chaperone; which may inhibit ER stress. It may be hypothesized that 4-PBA could attenuate via channels in DRG in diabetic neuropathy. Effects of 4-PBA were determined by applying different parameters of oxidative stress, cell viability, apoptosis assays and channel expression in cultured DRG neurons. Hyperglycemia-induced apoptosis in the DRG neuron was inhibited by 4-PBA. Cell viability of DRG neurons was not altered by 4-PBA. Oxidative stress was significantly blocked by the 4-PBA. Sodium channel expression was not altered by the 4-PBA. Our data provide evidence that the hyperglycemia-induced alteration may be reduced by the 4-PBA without altering the sodium channel expression.
authors: Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, 160 062, Punjab, India.
authors: Dilip
authors: D
authors: Sharma
authors: Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, 160 062, Punjab, India. Electronic address: jnsingh@niper.ac.in.
authors: Jitendra Narain
authors: JN
authors: Singh
authors: Electrophysiology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, 160 062, Punjab, India. Electronic address: sssharma@niper.ac.in.
authors: Shyam S
authors: SS
authors: Sharma
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010654:Phenylbutyrates / Q000494:pharmacology*; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley
chemical_list: D062559:NAV1.8 Voltage-Gated Sodium Channel; D010654:Phenylbutyrates; C568319:Scn10a protein, rat; C075773:4-phenylbutyric acid; D005947:Glucose
keywords: Diabetic neuropathy; Dorsal root ganglion; Hyperglycemia; Pain perception; Sodium channel expression