Upregulation of Thioredoxin Reductase 1 Expression by Flavan-3-Ols Protects Human Kidney Proximal Tubular Cells from Hypoxia-Induced Cell Death
Bibliographic record
Abstract
Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced cell death in renal tubular epithelial cells. Human kidney proximal tubular cells (HKC-8) were exposed to hypoxia (1% O2) in the presence of flavan-3-ols (catechin, epicatechin, procyanidin B1, and procyanidin B2). Cell death was examined using flow cytometric analysis. Gene expression was determined using a PCR array and Western blotting, and its network and functions were investigated using STRING databases. Here, we show that the cytoprotective activity of catechin was the highest among these flavan-3-ols against hypoxia-induced cell death in cultured HKC-8 cells. Exposure of HKC-8 cells to hypoxia induced oxidative stress leading to up-regulation of DUOX2, NOX4, CYBB and PTGS2 and down-regulation of TXNRD1 and HSP90AA1. Treatment with catechin or other flavan-3-ols prevented the down-regulation of TXNRD1 expression in hypoxic HKC-8 cells. Overexpression of TXNRD1 prevented hypoxia-induced cell death, and inactivation of TXNRD1 with TRi-1, a specific TXNRD1 inhibitor, reduced the catechin cytoprotection against hypoxia-induced HKC-8 cell death. In conclusion, flavan-3-ols prevent hypoxia-induced cell death in human proximal tubular epithelial cells, which might be mediated by their maintenance of TXNRD1 expression, suggesting that enhancing TXNRD1 expression or activity may become a novel therapeutic strategy to prevent hypoxia-induced kidney damage.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".