Oxidative stress-induced, poly(ADP-ribose) polymerase-dependent upregulation of ET-1 expression in chronic diabetic complicationsThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.
Bibliographic record
Abstract
Hyperglycemia in diabetes induces increased endothelin-1 (ET-1) production in the retina, kidney, and heart that may lead to hemodynamic impairment, permeability alteration, and increased extracellular matrix (ECM) protein production. Chronically elevated blood glucose levels may cause oxidative stress in these target tissues of diabetic complications. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme activated by DNA strand breaks due to oxidative stress. We investigated the role of PARP in regulating ET-1 expression and ET-1-induced abnormalities in the targets organs of diabetic complications. Male Sprague-Dawley rats were injected with streptozotocin to induce diabetes. Once diabetes was established, half of the diabetic rats were randomly chosen to receive PARP inhibitor 3-aminobenzamide for 4 months. In a second set of experiments, PARP-/- mice and their controls were fed for 2 months with either a normal rodent diet or a 30% galactose diet to induce a normoinsulinemic hyperhexosemic state. Tissues harvested at the conclusion of both experiments were then subjected to real-time RT-PCR analysis for mRNA expression and immunohistochemical assessment of oxidative stress. In both experiments, the hyperhexosemic state upregulated expression of ET-1 mRNA in the retina, kidney, and heart. Furthermore, upregulation of ET-1-dependent ECM transcripts, such as fibronectin and extradomain B-containing fibronectin, was noted in all tissues. These tissues also demonstrated oxidative stress, as evidenced by the presence of nuclei positive for 8-hydroxy-2'-deoxyguanosine. In contrast, inhibition of PARP, either through a chemical means in the diabetic rats or by genetic manipulation in the galactose-fed animals, prevented both oxidative stress and hyperhexosemia-induced upregulation of these genes. These results suggest that, in diabetes, oxidative stress and PARP activation may produce their effects through ET-1. Hence, blockade of such pathways may constitute potential adjuvant treatment modalities in chronic diabetic complications.
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) | 0.001 | 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".