Quercetin Attenuates Copper-Induced Apoptotic Cell Death and Endoplasmic Reticulum Stress in SH-SY5Y Cells by Autophagic Modulation

• Published in: Biological trace element research 2022-12, Vol.200 (12), p.5022-5041
• Main Authors: Chakraborty, Joyeeta, Pakrashi, Sourav, Sarbajna, Arpita, Dutta, Moumita, Bandyopadhyay, Jaya
• Format: Article
• Language: English
• Subjects: Agricultural products; Anthropogenic factors; Apoptosis; Autophagy; BAX protein; Bcl-2 protein; Biochemistry; Biomedical and Life Sciences; Biotechnology; Cell culture; Cell death; Cell lines; Condensates; Contamination; Copper; Cytochrome; Cytochrome-c oxidase; Cytochromes; Endoplasmic reticulum; Health risks; Heat shock proteins; Heavy metals; Homeostasis; Life Sciences; Membrane potential; Microtubules; Mitochondria; Movement disorders; Neuroblastoma; Neurodegeneration; Neurodegenerative diseases; Neurotoxicity; Nutrition; Oncology; Organelles; Oxidative stress; Parkinson's disease; Polyphenols; Proteins; Quercetin; Reactive oxygen species; Stress proteins; Toxicity
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-022-03093-x

An increase in anthropogenic activities results in metal contamination in the ecosystem which has proven to be a major health risk in humans, as they make entry into cellular organelles via agricultural products. Copper (Cu) is one such metal that acts as an essential cofactor for the activity of several enzymes, one being the cytochrome c oxidase. The increasing number of evidence suggests a substantial correlation of Cu overload with neurodegenerative disorders, including Parkinson’s disease (PD). We aim to explore quercetin, a well-known polyphenol, as an alternative for combating Cu-induced toxicity in human neuroblastoma SH-SY5Y secondary cell lines. We observed that Cu increased intracellular reactive oxygen species (ROS) levels, triggered morphological deformities and condensation of nuclei, caused an imbalance in the mitochondrial membrane potential (MMP), and finally induced apoptotic cell deaths. We further investigated the effects of Cu in modulating the pro- and anti-apoptotic proteins, such as Bax, Bcl-2, etc. However, quercetin reversed these changes owing to its antioxidant and anti-apoptotic properties, resulting in autophagy induction as an outcome of upregulation of autophagosome-bound microtubules-associated protein light chain-3 (LC3II). Besides, we investigated the role of Cu in stimulating ER stress proteins, viz. PERK, CHOP, and the concomitant responses of quercetin in restoring the ER homeostasis in cellular organelles like mitochondria and ER, against Cu-induced toxic insults by modulating autophagic pathways. Overall, this research work proposes a remedial approach for Cu-mediated neurotoxicity through understanding the diverse molecular signaling inside a cell with an aim to develop effective therapeutics.