Interplay of Vitamin D, Unfolded Protein Response, and Iron Metabolism in Neuroblastoma Cells: A Therapeutic Approach in Neurodegenerative Conditions

• Published in: International journal of molecular sciences Vol. 24; no. 23; p. 16883
• Main Authors: Jánosa, Gergely, Pandur, Edina, Pap, Ramóna, Horváth, Adrienn, Sipos, Katalin
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2023
• Subjects: Alfacalcidol; Analysis; Brain research; Calcifediol; cell culture; Cytokines; Cytokines - metabolism; Development and progression; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Gene expression; Genes; Health aspects; Homeostasis; Humans; Inflammation; Interleukins; Iron; Iron - metabolism; Metabolism; Nervous system; Nervous system diseases; Neuroblastoma; Neuroblastoma - drug therapy; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - metabolism; Oxidative stress; Physiological aspects; Protein expression; Protein folding; Proteins; SH-SY5Y; Signal transduction; Unfolded Protein Response; UPR; Vitamin D; Netherlands; Massachusetts; California; SH-SY5Y; unfolded protein response; iron; cell culture; UPR; vitamin D
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242316883

Vitamin D3 (VD) is crucial for various cell functions, including gene regulation, antioxidant defense, and neural health. Neurodegenerative conditions are closely linked to the unfolded protein response (UPR), a mechanism reacting to endoplasmic reticulum (ER) stress. Iron metabolism is intricately associated with UPR and neurodegeneration. This study used SH-SY5Y neuroblastoma cells to investigate the relationship between UPR, iron metabolism, and VD. Different sequences of treatments (pre- and post-treatments) were applied using VD and thapsigargin (Tg), and various methods were used for evaluation, including real-time qPCR, Western blotting, ELISA, and iron content analysis. The findings indicate that VD affects UPR pathways, cytokine release, and iron-related genes, potentially offering anti-inflammatory benefits. It also influences iron transporters and storage proteins, helping to maintain cellular iron balance. Furthermore, pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) were impacting UPR activation in cells. VD also influenced fractalkine ( ) gene expression and secretion, suggesting its potential as a therapeutic agent for addressing neuroinflammation and iron dysregulation. This research provides insights into the intricate connections among VD, UPR, and iron metabolism in SH-SY5Y neuroblastoma cells, with implications for future investigations and potential therapeutic approaches in neurodegenerative diseases characterized by UPR dysregulation and iron accumulation.