Renal phosphorylation of p44 mitogen-activated protein kinase and myosin light chain phosphatase targeting subunit 1 at Thr697 as cadmium-induced hypertension mechanisms
Notice bibliographique
Résumé
Objective: Cadmium (Cd) exposure is implicated in the pathogenesis of hypertension, a global non-communicable lifestyle disease which is reportedly mitigated by potassium supplementation. We aimed to induce hypertension in male Sprague-Dawley rats to investigate the mechanisms of Cd-induced hypertension and the mitigating effects of potassium supplementation since they are not fully elucidated. Hypothesis: We hypothesized that Cd induces hypertension through activation of extracellular signal-regulated kinase (ERK) pathways and inhibition of myosin light chain phosphatase (MLCP). METHOD: Six cohorts of control, Cd-exposed, and potassium-supplemented male Sprague-Dawley rats were selected. Hypertension was induced using cadmium chloride (2.5 or 5 mg/kg b.w.). Blood pressure, heart rate, and blood flow were measured twice weekly. Protein expressions were assessed in Cd-exposed rats for eight weeks via western blotting to determine the calcium handling effect and possible signaling pathways and underlying mechanisms involved. Data: Statistical analysis was done using one-way analysis of variance (ANOVA) and the results were reported as mean ± standard error of the mean. The Games-Howell or Bonferroni post hoc test was used for multiple comparisons. Summary of Results: Cd induced hypertension in vivo by significantly (p < 0.001) elevating blood pressures (mm Hg) [systolic (160 ± 2 and 155 ± 1 vs 120 ± 1), diastolic (119 ± 2 and 110 ± 1 vs 81 ± 1), mean arterial (133 ± 2 and 125 ± 1 vs 94 ± 1), and pulse (43 ± 1 and 45 ± 1 vs 39 ± 1; p < 0.05)], heart rate (507.2 ± 6.7 Cd 5 mg/kg b.w. vs 467.5 ± 7.5 beats/minute; p < 0.05), and flow rate (26.25 ± 1.20 and 28.28 ± 1.24 vs 18.02 ± 0.74 mL/L) while potassium supplementation conferred protection. The mechanism involved augmenting renal myosin light chain phosphatase targeting subunit 1 at threonine 697 (MYPT1-Thr697) (2.58 ± 0.36 vs 1 ± 0) and p44 mitogen-activated protein kinase (MAPK) (1.78 ± 0.20 vs 1 ± 0). Potassium supplementation significantly reduced this MYPT1-Thr697 phosphorylation. Conclusions: The results show that the hypertensive effects of Cd could be mediated by MLCP inhibition via phosphorylation of renal MYPT1-Thr697 and oxidative stress via p44 MAPK, an ERK. The importance of the kidneys in regulating blood pressure changes after Cd exposure and the mitigating effects of potassium supplementation are also emphasized. The kidneys should, therefore, be targeted for drug therapy in managing hypertension and further investigation of small arteries and Rho-kinase/MYPT1 interactions is recommended. Additionally, the study was limited by not challenging the tissues with a contractile agent for LC20 analysis and not being able to perform blots for Rho-kinase, so future studies should also include these two assessments. The Mona Campus Committee for Research and Publications and Graduate Awards, School for Graduate Studies and Research, The University of the West Indies This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, pas un consensus.
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