A264 AUTOPHAGY IS CRITICAL FOR GOBLET CELLS TO MAINTAIN HOMEOSTASIS UNDER HIGH METABOLIC STRESS
Bibliographic record
Abstract
Cellular stress induced by external or internal agents lead to the activation of several processes to maintain homeostasis. These processes involve the unfolded protein response (UPR), apoptosis and autophagy. Autophagy is a catabolic pathway that mediates the degradation of cellular components into double-membrane vesicle fused with lysosomes forming autolysosomes that lead to the removal of non-functional proteins and organelles. Goblet cells in the gut secrete MUC2 mucin to form the mucus layers which serves as a protective barrier against invading microbes and noxious substances. Autophagy has been suggested to play a role in the regulation of mucin secretion and cell survival by an unknown mechanism. AMPK has been shown to be an essential mediator to activate autophagy through mTOR inhibition to maintain metabolic homeostasis and cell survival. As goblet cells undergo increased ER stress to produce MUC2 mucin under inflammatory and disease conditions we hypothesize that autophagy plays a role in MUC2 degradation and/or cell survival. To quantify the autophagy response and AMPK signaling in high and low MUC2 producing HT29 cells. High MUC2-producing human HT29-H cells and a clone of HT29-H silenced for MUC2 (HT29-L) by lentivirus shRNA was used in the study. Autophagy proteins were evaluated in HT29H/L cells by Western blot using monoclonal antibodies for ULK1 and their phospho-antibodies. AMPK signaling was quantified by anti-AMPKα antibody. Autophagy and AMPK genes were quantified transcriptionally by RT-PCR. Acadesine (AICAR) and Torin1 was used to activate AMPK signaling and autophagy respectively. High MUC2 producing HT29-H cells under metabolic stress accumulated misfolded MUC2 proteins and impaired basal autophagy protein expression (LC3-II and ULK1) as compared to HT29-L cells. Basal phosphorylation of pULK1(S555) was upregulated through an AMPK-mediated mechanism in HT29-H cells whereas pAMPKα (T172) was downregulated in HT29-L cells. Cells stimulated with the AMPK agonist, acadesine (AICAR), enhanced pAMPKα (T172) and ULKI phosphorylation in HT29-H but not HT29-L cells. Similarly, stimulation with Torin1 (an autophagy inducer) increased the expression of AMPKα and ULK1 in HT29-H but not HT29-L cells. These results suggest that the impaired phosphorylation events in autophagy and AMPK signaling in HT29-H may lead to perturbed homeostasis. The interplay between autophagy with AMPK signaling helps to maintain homeostasis in intestinal epithelial cells. This study demonstrates that impaired autophagy in high MUC2 mucin-producing cells might be a cellular defense to enhance cell survival. CCC
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.004 | 0.002 |
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".