Caveolin 1 ameliorates nonesterified fatty acid–induced oxidative stress via the autophagy regulator beclin 1 in bovine mammary gland epithelial cells
Bibliographic record
Abstract
High blood concentrations of nonesterified fatty acids (NEFA) during ketosis enhance uptake by the mammary gland and impair autophagy while causing oxidative stress. Caveolin 1 (CAV1) is closely related to autophagy and plays a role in regulating oxidative stress. The aim of this study was to explore the potential role of CAV1 on oxidative stress and autophagy during a high-NEFA challenge in the immortalized bovine mammary epithelial cell line (MAC-T). Mammary gland tissue biopsies and blood samples were collected from healthy (n = 15) and clinically ketotic (n = 15) Holstein cows at 3 to 10 (average = 6) days in milk. Compared with healthy cows, ketotic cows had lower DMI, daily milk yield, and serum glucose, and greater serum NEFA and BHB, accompanied by greater milk fat and lower milk protein. Malondialdehyde (MDA) was greater, but activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase were lower in cows with clinical ketosis. A lower protein abundance of CAV1, beclin 1, autophagy relative gene 5 (ATG5), and microtubule-associated protein 1 light chain 3 (LC3) as well as greater protein abundance of sequestosome-1 (SQSTM1, also called p62) were detected in mammary tissue of cows with clinical ketosis. In vitro, the MAC-T cells were treated with 0, 0.6, and 1.2 mM NEFA for 12 h or treated with 1.2 mM NEFA for various lengths of time (0, 0.5, 1, 2, 4, 8, 12, and 24 h). Compared with 0 mM NEFA, protein abundances of CAV1, beclin 1, ATG5, and LC3 were greater in the MAC-T challenged with 0.6 mM NEFA but lower in the 1.2 mM NEFA group. Protein abundance of p62 was lower with 0.6 mM NEFA but higher with 1.2 mM NEFA. In response to increasing doses of NEFA, mRNA abundance of CAV1, total antioxidant capacity and SOD activity decreased, whereas the levels of reactive oxygen species and MDA content increased. The protein abundances of CAV1 and beclin 1 peaked at 0.5 h, the protein abundances of ATG5 and LC3 peaked at 1 h, and these proteins start to fade away at later time points under NEFA treatment, resulting in both linear and quadratic effects. The protein abundance of p62 decreased, reaching a nadir at 4 h in both a linear and quadratic manner. The silencing of CAV1 in MAC-T cells aggravated the 1.2 mM NEFA-induced decrease in beclin 1 expression, impaired autophagy, and increased severe oxidative stress, whereas the overexpression of CAV1 alleviated these effects. Pretreatment of MAC-T cells with beclin 1 small interfering RNA (si-beclin 1) and the overexpression of CAV1, followed by challenge with 1.2 mM NEFA, resulted in reversed CAV1-induced autophagy, thereby aggravating oxidative stress. Overall, these data suggest that CAV1 protects bovine mammary epithelial cells from NEFA-induced oxidative stress through enhancing the expression of beclin 1 and activating autophagy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".