Role of mitochondria in rabies virus-induced oxidative stress
Notice bibliographique
Résumé
Neuronal process degeneration occurs in an experimental mouse model of rabies with hindlimb footpad inoculation of the challenge virus standard-11 (CVS) strain. CVS infection of primary mouse and rat dorsal root ganglion (DRG) neurons has associated axonal degeneration with axonal swellings and neurite outgrowth reduction. The CVSinduced axonal swellings feature protein adducts of 4-hydroxy-2-nonenal (4-HNE), a marker for lipid peroxidation, indicating a critical role of oxidative stress. Western immunoblotting analysis indicated that adducts of 4-HNE expression is also increased in the CVS-infected rat adrenal medulla (PC12) cell line. Mitochondrial dysfunction is one of the most important causes for overproduction and accumulation of reactive oxygen species (ROS). We investigated the effects of CVS infection on several mitochondrial parameters in different cell types (DRG primary neurons, PC12, mouse neuroblastoma (MNA), and baby hamster kidney (BHK-S13) cells) at 72 hrs post infection. The biochemical activity of electron transport system (ETS) complexes (I, IIIII, and IV) and Krebs cycle enzymes (citrate synthase and malate dehydrogenase) were evaluated using a spectrophotometric approach. Krebs cycle enzyme activities were not affected in CVS- versus mock-infected cells. Complex I activity was significantly increased in all CVS-infected cells versus mock-infected controls. Complex I was increased by 30-35% in CVS-infected DRG and PC12 cells, whereas it was increased by 65-75% in MNA and BHK-S13 cells. These values were proportional to the susceptibility of the cells to CVS infection suggesting a direct effect of the CVS infection on Complex I. Complex II-III activity was normal in the infected cells. Complex IV activity was upregulated in all types of CVSinfected cells. However, the increase did not relate to the susceptibility of the cells to the infection, suggesting an indirect effect. We postulate that enhanced Complex IV activity in CVS-infected cells may play a role in avoiding apoptosis. NADH, which is a Complex I-substrate, level was significantly higher in CVS-infected versus mock-infected PC12 cells. NAD+ level in CVS-infected PC12 cells was similar to that in mock-infected controls. Despite the increased activity of ETS complexes, CVS infection reduced the intracellular level of ATP in PC12 cells. The reduced ATP level in CVS-infected DRG neurons may explain, at least in part, the reduction in the neurite outgrowth that was previously observed. We predict that a high mitochondrial inner membrane potential is generated in CVS infection because of increased proton pumping across the mitochondrial inner membrane due to higher activity of Complex I and IV, and decreased proton consumption as indicated by reduced intracellular ATP level. Induction of a high mitochondrial membrane potential promotes electron leakage, primarily at the Complex I site, leading to ROS overgeneration and oxidative stress.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
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; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».