Neuroprotective effect of quercetin against radiation‐induced endoplasmic reticulum stress in neurons

Abstract

The endoplasmic reticulum (ER) plays an important role in the regulation and maintenance of cellular homeostasis. However, unresolved ER stress leads to deleterious effects by inducing the accumulation of unfolded proteins in the cell. Here we have demonstrated the protective aspects of quercetin against radiation-induced ER stress and against inflammation in primary cultured dorsal root ganglion (DRG) neurons. The mature DRG neurons were pretreated with different concentrations of quercetin (5-100 μM) for 24 hours before 2 Gy gamma radiation exposure and then subjected to a cytotoxicity assay, quantitative real-time polymerase chain reaction and Western blot analysis. The results showed that quercetin decreased the expression of BiP and C/EBP-homologous protein, the ER stress marker genes along with downregulation of tumor necrosis factor-α, JNK in irradiated DRG neurons. Furthermore, quercetin pretreatment significantly increased the cytoskeletal protein Tuj1 and the neurotrophin brain-derived neurotrophic factor in the neuron. These results indicate that quercetin plays a neuroprotective role against radiation-mediated ER stress and inflammatory responses. K E Y W O R D S dorsal root ganglion (DRG) neuron, endoplasmic reticulum (ER) stress, gamma radiation, inflammation, quercetin J Biochem Mol Toxicol. 2019;33:e22242.wileyonlinelibrary.com/journal/jbt

[Retracted] Quercetin Prevents Radiation‐Induced Oral Mucositis by Upregulating BMI‐1

“…ROS and DNA damage activate NF- κ B to stimulate the release of proinflammatory cytokines, e.g., TNF- α , TGF- β , IL-6, and IL-1 β . Quercetin can inhibit TGF- β expression in irradiated mouse skin [ 13 ] and can reduce TNF- α expression in irradiated rat colon [ 12 ] and primary cultured dorsal root ganglion neurons [ 10 ]. Quercetin downregulates the Src/PI3K/Akt-NF- κ B-inflammatory pathways to attenuate atherosclerosis progression [ 25 ] and protects the skin from UVB-induced damage by inhibiting the NF- κ B/COX-2 signaling pathway [ 26 ].…”

Radioprotective Effect of Flavonoids on Ionizing Radiation-Induced Brain Damage

“…It reduced the expression of the endoplasmic reticulum stress marker gene in irradiated DRG neurons and downregulated the expression of TNF-α. Furthermore, it significantly increased the expression of the Tuj1 protein, suggesting neuronal revival, and decreased the apoptotic markers C/EBP-homologous protein (CHOP), jun-N-terminal kinases (JNK) and pJNK protein levels [85]. No toxicity was reported at the concentration used [22,85].…”

“…Furthermore, it significantly increased the expression of the Tuj1 protein, suggesting neuronal revival, and decreased the apoptotic markers C/EBP-homologous protein (CHOP), jun-N-terminal kinases (JNK) and pJNK protein levels [85]. No toxicity was reported at the concentration used [22,85]. However, quercetin is a well-known flavonoid with low bioavailability.…”

Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products

“…The quercetin derivatives obtained from apple tree leaves showed a significant neuroprotective effect at low concentrations of 0.5-1.0 mg/L as compared to other phytoconstituents [137]. The results presented by Chatterjee et al [138] revealed the neuroprotective importance of quercetin in treating dorsal root ganglion (DRG) neurons exposed to radiation-induced ER stress. The neuroprotective role of quercetin against oxidative stress-related neurodegenerative ailments in cortical brain tissue cultures from Wister rats was studied [139].…”