β‑Carotene Ameliorates LPS-Induced Endoplasmic Reticulum Stress and Mitochondrial Disorder by Targeting ORAI1 in Bovine Mammary Epithelial Cells

• Published in: Journal of agricultural and food chemistry 2024-12, Vol.72 (48), p.26733-26745
• Main Authors: Meng, Meijuan, Li, Xuerui, Zhou, Shendong, Shi, Xiaoli, Shen, Xiangzhen, Chang, Guangjun
• Format: Article
• Language: English
• Subjects: Animals; beta Carotene - pharmacology; Bioactive Constituents, Metabolites, and Functions; Calcium - metabolism; Cattle; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Female; Lipopolysaccharides - adverse effects; Lipopolysaccharides - pharmacology; Mammary Glands, Animal - cytology; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; ORAI1 Protein - genetics; ORAI1 Protein - metabolism
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.4c06875

Ca2+ is an important regulator of endoplasmic reticulum (ER) and mitochondrial function. Store-operated calcium entry (SOCE) serves as the predominant pathway for the influx of extracellular Ca2+ into the cell. ORAI1, ORAI2, and ORAI3 are the main proteins of SOCE. Ca2+ disturbance leads to ER stress and mitochondrial damage. β-Carotene (β-C) is a precursor of vitamin A and has anti-inflammatory and antioxidant effects. However, it remains unclear if β-C mitigates ER stress and mitochondrial dysfunction triggered by LPS and its underlying molecular mechanisms have not been fully elucidated in bovine mammary epithelial cells (BMECs). Therefore, the experiment aimed to explore the protective mechanism of β-C. Results showed that LPS increased the ORAI1 expression, and caused ER stress by upregulating the expression of ER stress-related genes and proteins in BMECs. LPS also caused mitochondrial dysfunction by decreasing mitochondrial fusion proteins and increasing mitochondrial division and apoptosis proteins. Silencing ORAI1 mitigated ER stress and mitochondrial impairment caused by LPS. Conversely, elevated ORAI1 levels induced similar stress and damage in BMECs. β-C pretreatment resulted in diminished ORAI1 expression and a reduction in ER stress and mitochondrial dysfunction triggered by LPS. However, ORAI1 overexpression blocked the protective effects of β-C. In conclusion, β-C alleviated the LPS-induced ER stress and mitochondria dysfunction in an ORAI1-dependent manner. Our findings provide a mechanistic basis for further exploration of the regulatory effects of β-C on mammary injuries.