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Article

5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells

1
Department of Biomedical Engineering, Graduate School of Medicine, Science and Technology, Shinshu University, Minamiminowa, Kamiina-gun, Nagano 399-4598, Japan
2
Department of Biomedical Engineering, Graduate School of Science and Technology, Shinshu University, Minamiminowa, Kamiina, Nagano 399-4598, Japan
3
Neopharma Japan Co., Ltd., Tokyo 102-0071, Japan
4
Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan
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Department of Biomolecular Innovation, Institute for Biomedical Sciences, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Daniele Vergara
Molecules 2021, 26(4), 1183; https://doi.org/10.3390/molecules26041183
Received: 25 December 2020 / Revised: 19 February 2021 / Accepted: 19 February 2021 / Published: 23 February 2021
The conservation of mammary gland physiology by maintaining the maximum number of mammary epithelial cells (MECs) is of the utmost importance for the optimum amount of milk production. In a state of negative energy balance, palmitic acid (PA) reduces the number of bovine MECs. However, there is no effective strategy against PA-induced apoptosis of MECs. In the present study, 5-aminolevulinic acid (5-ALA) was established as a remedial agent against PA-induced apoptosis of MAC-T cells (an established line of bovine MECs). In PA-treated cells, the apoptosis-related genes BCL2 and BAX were down- and upregulated, respectively. The elevated expression of major genes of the unfolded protein response (UPR), such as CHOP, a proapoptotic marker (C/EBP homologous protein), reduced the viability of PA-treated MAC-T cells. In contrast, 5-ALA pretreatment increased and decreased BCL2 and BAX expression, respectively. Moreover, cleaved caspase-3 protein expression was significantly reduced in the 5-ALA-pretreated group in comparison with the PA group. The downregulation of major UPR-related genes, including CHOP, extended the viability of MAC-T cells pretreated with 5-ALA and also reduced the enhanced intensity of the PA-induced expression of phospho-protein kinase R-like ER kinase. Moreover, the enhanced expression of HO-1 (antioxidant gene heme oxygenase) by 5-ALA reduced PA-induced oxidative stress (OxS). HO-1 is not only protective against OxS but also effective against ER stress. Collectively, these findings offer new insights into the protective effects of 5-ALA against PA-induced apoptosis of bovine MECs. View Full-Text
Keywords: 5-ALA; palmitic acid; bovine mammary epithelial cell; ER stress; oxidative stress 5-ALA; palmitic acid; bovine mammary epithelial cell; ER stress; oxidative stress
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MDPI and ACS Style

Sharmin, M.M.; Islam, M.A.; Yamamoto, I.; Taniguchi, S.; Yonekura, S. 5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells. Molecules 2021, 26, 1183. https://doi.org/10.3390/molecules26041183

AMA Style

Sharmin MM, Islam MA, Yamamoto I, Taniguchi S, Yonekura S. 5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells. Molecules. 2021; 26(4):1183. https://doi.org/10.3390/molecules26041183

Chicago/Turabian Style

Sharmin, Mst M., Md A. Islam, Itsuki Yamamoto, Shin Taniguchi, and Shinichi Yonekura. 2021. "5-ALA Attenuates the Palmitic Acid-Induced ER Stress and Apoptosis in Bovine Mammary Epithelial Cells" Molecules 26, no. 4: 1183. https://doi.org/10.3390/molecules26041183

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