Participação do estresse de retículo endoplasmático no processo de morte celular em neutrófilos de ratos diabéticos.
Notice bibliographique
Résumé
Endoplasmic reticulum (ER) has been gaining evidence when it comes to cell death.This organelle may go under stress conditions due to changes in protein formation, lack of ATP, disturbances in calcium signaling and alterations in the redox state.The accumulation of unfolded proteins initiates the activation of the Unfolded Protein Response (UPR).Currently, it is well established that the ER stress response is due to activation of three ER components: Inositol-Requiring kinase 1α (IRE1α), double-stranded RNA-activated protein kinase-like ER kinase (PERK) and Activating transcription factor 6 (ATF6).The UPR may resolve the ER stress by upregulating genes responsible to maintain the ER homeostasis; or it can activate genes that lead to the cell death when the ER disbalance is not solved.Hyperglycemia, one of many symptoms observed is Diabetes, may cause ER stress in various types of cells, for instance, pancreatic β-cells, osteoblasts and cardiomiocytes.Thus, this study aims to investigate the possible involvement of the ER stress in the process of cell death in neutrophils from diabetic rats.ER stress was evaluated by the expression of key genes: GRP78 (Bip), IRE-1, PERK, ATF-6 by PCR real time; the content of proteins related to the PERK pathway: PERK, eIF2α, peIF2α, ATF4, CHOP and GADD34; the content o pJNK, a protein related to cell death that is activated by IRE1α pathway; the content of ATF6 and sXBP1 resulted from the IRE1α activity.Also, the gene expression of MAM proteins related to the association between ER and mitochondria, Mitofusin 2, GRP75 and PACS2, were evaluated.MAM is related to the ER homeostasis and is very importat for calcium and ATP exechange between these twoorganelles.Finally, activity of caspases 3 by spectrofluorimetry and ROS production by chemoluminescence, using luminol, were measured.We observed higher expression of GRP78 (Bip) in the control group and higher expression of IRE1α in the diabetic and control group when they were stimulated with PMA.However, increase in IRE1α was observed in the non-stimulated state only in the diabetic group.This same pattern was observed in CHOP gene expression.The content of peIF2α was higher in the control group without stimulus and the other proteins of the PERK pathway showed no alteration.Gene expression of the MAM proteins was higher in the control group when neutrophils were stimulated with PMA.CHOP content was increased in the diabetic group.Finally, Caspase 3 activity and the reason Bax/Bcl2 were higher in the diabetic group stimulated with PMA.In summary, our study found that neutrophils from diabetic rats when stimulated with PMA exhibit greater susceptibility to death due to activation of IRE1α and subsequent phosphorylation of JNK, reduced safety in mitochondria-ER interaction in the MAM compartment and increased caspase-3 activation.We also conclude that these changes were not altered by ROS, since the two groups, control and diabetic, have the same profile of these species production when stimulated with PMA.Control group seems to be protect against the ER stress by ROS production by higher expression of GRP78 and MAM proteins.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».