ArticleMetabolites2022
Non-Esterified Fatty Acid Induces ER Stress-Mediated Apoptosis via ROS/MAPK Signaling Pathway in Bovine Mammary Epithelial Cells.
Article in Metabolites, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Betaine Promotes Milk Protein Synthesis via Alleviating Oxidative Stress Caused by NEFA in Mammary Epithelial Cells of Dairy Cows.Veterinary medicine and science · 2026Article
- Metabolic adaptive role of interleukin-15 in postpartum dairy cows with negative energy balance.Open veterinary journal · 2026Article
- Choline as a Modulator of Periparturient Diseases in Dairy Cows.Veterinary sciences · 2025Review
- NDUFAB1 as a Novel Regulator of NEFA-Induced Metabolic Dysfunction in Bovine Adipocytes.Animals : an open access journal from MDPI · 2025Article
- Isorhamnetin Ameliorates Non-Esterified Fatty Acid-Induced Apoptosis, Lipid Accumulation, and Oxidative Stress in Bovine Endometrial Epithelial Cells via Inhibiting the MAPK Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Resveratrol Alleviates NEFA-Induced Oxidative Damage in Bovine Mammary Epithelial Cells by Restoring Mitochondrial Function.Animals : an open access journal from MDPI · 2025Article
- Study on the Antitumor Mechanism of Tanshinone IIA In Vivo and In Vitro through the Regulation of PERK-ATF4-HSPA5 Pathway-Mediated Ferroptosis.Molecules (Basel, Switzerland) · 2024Article
- Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2024Article
- Non-Esterified Fatty Acid-Induced Apoptosis in Bovine Granulosa Cells via ROS-Activated PI3K/AKT/FoxO1 Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- Enhancing bovine immune, antioxidant and anti-inflammatory responses with vitamins, rumen-protected amino acids, and trace minerals to prevent periparturient mastitis.Frontiers in immunology · 2023Review
- Transcriptome Analysis Reveals That NEFA and β-Hydroxybutyrate Induce Oxidative Stress and Inflammatory Response in Bovine Mammary Epithelial Cells.Metabolites · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Elevated concentrations of non-esterified fatty acid (NEFA) induced by negative energy balance (NEB) during the transition period of dairy cows is known to be toxic for multiple bovine cell types. However, the effect of NEFA in bovine mammary epithelial cells (BMECs) remains unclear. The present study aimed to explore the role and molecular mechanism of NEFA in endoplasmic reticulum (ER) stress and the subsequent apoptosis in BMECs. The results showed that NEFA increased ER stress and activated the three unfolded protein response (UPR) signaling sub-pathways by upregulating the expression of GRP78, HSP70, XBP1, ATF6, phosphor-PERK, and phosphor-IRE1α. We also found that NEFA dose-dependently induced apoptosis in BMECs, as indicated by flow cytometry analysis and increased apoptotic gene expression. RNA-seq analysis revealed that NEFA induced apoptosis in BMECs, probably via the ATF4-CHOP axis. Mechanistically, our data showed that NEFA increased reactive oxygen species (ROS) levels, resulting in the activation of the MAPK signaling pathway. Moreover, quercetin, a well-known antioxidant, was found to alleviate ER stress-mediated apoptosis in NEFA-treated BMECs. Collectively, our results suggest that NEFA induces ER stress-mediated apoptosis, probably via the ROS/MAPK signaling pathway, as quercetin has been shown to alleviate ER stress-mediated apoptosis in NEFA-treated BMECs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.