Phosphorylation of AktSer473/Ask1Ser83 in Trolox-induced suppression of doxorubicin-induced changes in rat cardiomyocytes
Bibliographic record
Abstract
OBjECTIvE:To examine the modulatory effects of the antioxidant Trolox in the interplay of Akt and apoptosis signal-regulating kinase (Ask) 1 in doxorubicin (Dox)-induced oxidative stress (OS).METHODS: Rat cardiomyocytes were treated with Dox (5 µM) or Trolox (20 µM) for 24 h, or were pretreated with Trolox (20 µM) for 4 h before treatment with Dox (5 µM) for 24 h, and were compared with cardiomyocytes without any treatment.For the Akt inhibition study, cardiomyocytes were pretreated overnight with the phosphoinositol 3-kinase/Akt inhibitor wortmannin (1 µM) before treatment with Dox, Trolox or Trolox + Dox.The gain and loss of Akt gene function with HA-tagged constitutively active Akt1 or dominant-negative mutant Akt1 (T308A; S473A) was also studied in the cardiomyocytes under all treatment conditions.Cells exposed to various treatment conditions were analyzed for OS, apoptotic and antiapoptotic proteins, and phosphorylation of Ask1 Ser83 , Ask1 Thr845 and Akt Ser473 .RESuLTS: Dox caused a decrease in the phosphorylation of Akt Ser473 .The phosphorylation of Ask1 was differentially modulated by Dox: Ask1 phosphorylation was upregulated at Thr845 sites and was downregulated at Ser83 sites.The levels of apoptotic proteins were also increased.Trolox pretreatment downregulated Dox-induced OS, promoted the activation of Akt Ser473 , and modulated Dox-induced changes in the phosphorylation of Ask1 and apoptosis-related proteins.Inhibition of phosphoinositol 3-kinase/Akt using wortmannin and dominant-negative Akt1 adenovirus promoted phosphorylation of Ask Thr845 and attenuated the phosphorylation of Ask1 Ser83 .In contrast, upregulation of Akt activity using constitutively active Akt1 promoted phosphorylation of Ask1 Ser83 and inhibited phosphorylation of Ask1 Thr845 , respectively.COnCLuSIOnS: Suppression of the effects of Dox by Trolox in rat cardiomyocytes occurs through the upregulation of Akt and its consensus site Ask1 Ser83 .
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".