Protein kinase Cθ activity is involved in the 2,3,7,8‐tetrachlorodibenzo‐<i>p</i>‐dioxin‐induced signal transduction pathway leading to apoptosis in L‐MAT, a human lymphoblastic T‐cell line
Bibliographic record
Abstract
The aromatic hydrocarbon receptor (AhR)-dependent pathway involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity has been studied extensively, but the AhR-independent molecular mechanism has not. In previous studies we found that the AhR is not expressed in L-MAT, a human lymphoblastic T-cell line. In this report, we provide the following evidence that the protein kinase C (PKC)theta activity is functionally involved in the AhR-independent signal transduction mechanism that participates in the TCDD-induced L-MAT cell apoptosis. First, only rottlerin, a novel PKC (nPKC)-selective inhibitor, blocked the apoptosis completely, in a dose-dependent manner. Second, PKCtheta was the major nPKC isoform (compared to PKCdelta) expressed in the L-MAT cell line. Third, a cell-permeable myristoylated PKCtheta pseudosubstrate peptide inhibitor also blocked the apoptosis completely, in a dose-dependent manner. Fourth, both rottlerin and myristoylated PKCtheta pseudosubstrate peptide inhibitor completely inhibited PKCtheta kinase activity in vitro at doses that effectively blocked TCDD-induced L-MAT cell apoptosis. TCDD treatment induced a time-dependent activation of nPKC kinase activity in L-MAT cells, and moreover, TCDD induced a translocation of PKCtheta from the cytosolic fraction to the particulate fraction in L-MAT cells. Finally, transient over-expression of a dominant negative PKCtheta (a kinase-dead mutant, K/R 409) in L-MAT cells conferred significant protection against TCDD-induced apoptosis.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".