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- Title
Palmitic acid-induced cell death: impact of endoplasmic reticulum and oxidative stress, mitigated by L-citrulline.
- Authors
Habib, Md. Rezwanul; Yukako Tokutake; Shinichi Yonekura
- Abstract
Objective: Palmitic acid (PA), the most abundant saturated free fatty acids, induces apoptosis in bovine mammary epithelial cells (MECs). It is suggested that oxidative stress and endoplasmic reticulum (ER) stress are key mechanisms underlying PAinduced cell death. This study aimed to investigate the interaction between ER stress and oxidative stress during PAinduced cell death in mammary alveolar cellT (MACT) cells. Additionally, we examined whether Lcitrulline can protect against PAinduced damage of MACT cells. Methods: MACT cells were treated with 4phenyl butyric acid (4PBA) or NacetylLcysteine (NAC) to inhibit PAinduced ER stress and oxidative stress, respectively. MACT cells were pretreated with or without Lcitrulline for 48 h followed by PA treatment. Cell viability was measured with MTT assays. Intracellular reactive oxygen species (ROS) levels in MACT cells were assessed using 5( and6) chloromethyl2', 7'dichlorodihydrofluores cein diacetate acetyl ester dye. Realtime quantitative polymerase chain reaction was used to explore the regulation of genes associated with oxidative stress, and ER stress genes. Western blotting analysis was also carried out. Results: 4PBA significantly reduced PAinduced mRNA expressions of activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), nuclear factor (erythroidderived 2)like 2 (NRF2), and intracellular ROS levels. Furthermore, NAC dramatically reduced PAinduced ROS levels and the mRNA expressions of NRF2, ATF4, and CHOP. Lcitrulline pretreatment effectively rescued cell viability decreased by PA. Moreover, Lcitrulline pretreatment significantly downregulated the PAinduced upregulation of GRP78, ATF4, and CHOP mRNA expression, and protein expression of pPERK and cleaved caspase3. PA increased intracellular ROS levels and NRF2 mRNA expression, whereas Lcitrulline pretreatment remarkably reduced these levels. Conclusion: Both ER and oxidative stresses interact during PAinduced cell death in MACT cells, and Lcitrulline could attenuate this cell death by inhibiting ER and oxidative stresses. Therefore, Lcitrulline may be a promising supplement for protecting against PAinduced cell death in bovine MECs during the lactation period of dairy cows.
- Subjects
TRANSCRIPTION factors; SATURATED fatty acids; FREE fatty acids; BUTYRIC acid; CELL death; PALMITIC acid
- Publication
Animal Bioscience, 2025, Vol 38, Issue 1, p54
- ISSN
2765-0189
- Publication type
Academic Journal
- DOI
10.5713/ab.24.0249