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. 2022 Dec;44(12):1565-1576.
doi: 10.1007/s13258-022-01256-7. Epub 2022 May 14.

1, 25-(OH)2D3 protects against ER stress and miRNA dysregulation in Mus musculus neurons

Parvathy Jayachandran  1 , Linda Koshy  2 , Perumana R Sudhakaran  2 , Govindapillai Mohanadasan Nair  2 , Appukuttan Nair Gangaprasad  2   3 , Ananthakrishnan Jayakumaran Nair  2
Affiliations

1, 25-(OH)2D3 protects against ER stress and miRNA dysregulation in Mus musculus neurons

Parvathy Jayachandran et al. Genes Genomics. 2022 Dec.

Abstract

Background: The pathophysiology of neurodegenerative diseases (NDDs) is closely associated with cellular oxidative stress which can result in the accumulation of toxic proteins in the endoplasmic reticulum (ER) leading to ER stress and subsequent unfolded protein response (UPR) signaling, a mechanism that aggravate these disorders. Vitamin D has been suggested to have important neuroprotective role and its administration has been shown to reduce neuronal injury, neurotoxicity and oxidative stress in various animal systems.

Objective: The current study was undertaken to examine the effect of vitamin D3 on UPR in ER stress induced Mus musculus neuronal cells.

Methods: Mus musculus cortical and hippocampal primary neuronal cultures were pretreated with 1,25-dihydroxyvitamin D3 (1, 25-(OH)2D3), the active form of vitamin D, followed by ER stress induction with a chemical ER stress inducer thapsigargin and with an advanced glycated protein, AGE-BSA. The UPR genes and related microRNAs (miRNA) expressions were analyzed mainly using real-time PCR.

Results: The experiment resulted in the suppression of ER stress marker BiP and UPR pathway genes such as Perk, Ire1α, Chop and Puma which mediate cellular apoptosis indicating the protective effect of 1, 25-(OH)2D3 against neuronal ER stress. Further studies into the molecular aspects showed that ER stress mediated down-regulated expression of microRNAs (miRNAs) such as mmu-miR-24, 27b, 124, 224, 290, 351 and 488 which are known to regulate the UPR pathway genes were also reduced with vitamin pretreatment, of which the miRNAs miR-24 and 27b which shares the same cluster are potentially involved in various human diseases.

Conclusion: This study emphasizes the therapeutic role of vitamin D in reducing neuronal ER stress and the need for maintaining sufficient amount of this vitamin in our diet.

Keywords: 1, 25-(OH)2D3; Advanced glycated end-products (AGEs); MicroRNA; Primary neuronal culture; Real-time PCR; Unfolded protein response.

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