Effect of oxidative stress on TRPM2 and TRPC3 channels in B lymphoblast cells in bipolar disorder
Bibliographic record
Abstract
OBJECTIVES: Recent findings implicate the calcium-permeable nonselective ion channels transient receptor potential (TRP) melastatin subtype 2 (TRPM2) and canonical subtype 3 (TRPC3) in the pathogenesis of bipolar disorder (BD). These channels are involved in calcium and oxidative stress signaling, both of which are disrupted in BD. Thus, we sought to determine if these channels are differentially affected by oxidative stress in cell lines of BD patient origin. METHODS: B lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) patients (n = 6) and healthy controls (n = 5) were challenged with the oxidative stressor rotenone (2.5 μM and 10 μM) or vehicle for acute (24 hours) and chronic (four days) intervals. Cell viability was measured using propidium iodide, while TRPM2- and TRPC3-mediated calcium fluxes were measured in the presence of their respective activators (H(2) O(2) and 1-oleoyl-2-acetyl-sn-glycerol) using Fluo-4. Changes in TRPM2 and TRPC3 expression levels were determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: Cell viability decreased with increasing dose and duration of rotenone treatment, with BD-I patient BLCLs more susceptible than controls acutely (p < 0.001). A dose-dependent decrease in TRPC3 protein expression occurred after chronic (24%, p = 0.008) but not acute rotenone treatment. Interestingly, H(2) O(2) -provoked TRPM2-dependent calcium fluxes revealed an interaction between the effects of stressor addition and diagnostic subject group (p = 0.003). CONCLUSIONS: These data support an important role for TRPM2 and TRPC3 in sensing and responding to oxidative stress and in transducing oxidative stress signaling to intracellular calcium homeostasis and cellular stress responses, all of which have been implicated in the pathophysiology of BD.
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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 | 0.001 |
| 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".