Lasmiditan restores mitochondrial quality control mechanisms and accelerates renal recovery after ischemia-reperfusion injury.
Acute kidney injury
Mitochondrial biogenesis
Mitochondrial dynamics
Mitochondrial dysfunction
Mitophagy
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
09
06
2023
revised:
01
10
2023
accepted:
11
10
2023
medline:
4
12
2023
pubmed:
23
10
2023
entrez:
22
10
2023
Statut:
ppublish
Résumé
Mitochondrial dysfunction is a well-established result of acute kidney injury (AKI). Previously, we identified that 5-hydroxytryptamine 1F (5-HT Male mice were subjected to renal ischemia/reperfusion (I/R) and treated daily with lasmiditan (0.3 mg/kg) or vehicle beginning 24 h after injury for 3 or 6d. Serum creatinine was measured to estimate glomerular filtration. Electron microscopy was used to assess mitochondrial morphology and mitophagy. Mitochondrial-related protein were confirmed with immunoblotting. Mitochondrial function was assessed with ATP measurements. Lasmiditan treatment improved mitochondrial and kidney recovery as early as 3d post-AKI, as evidenced by increased ATP, and decreased serum creatinine, respectively. Electron micrographs of renal cortices revealed that lasmiditan also decreased mitochondrial damage and increased mitochondrial area and size by 6d after I/R injury. Additionally, lasmiditan treatment increased mitolysosomes by 3d, indicating induction of mitophagy. Phosphorylation of mitophagy-related proteins were also increased in the renal cortices of lasmiditan-treated AKI mice 3d after I/R injury, whereas fusion-related proteins were increased at 6d after I/R injury. These data reveal that lasmiditan accelerates renal recovery, restores normal mitochondrial membrane and cristae morphology, decreases excessive mitochondrial fission, and accelerates mitophagy post-AKI in a time-dependent manner, establishing mitochondrial function and recovery from AKI.
Sections du résumé
BACKGROUND
BACKGROUND
Mitochondrial dysfunction is a well-established result of acute kidney injury (AKI). Previously, we identified that 5-hydroxytryptamine 1F (5-HT
METHODS
METHODS
Male mice were subjected to renal ischemia/reperfusion (I/R) and treated daily with lasmiditan (0.3 mg/kg) or vehicle beginning 24 h after injury for 3 or 6d. Serum creatinine was measured to estimate glomerular filtration. Electron microscopy was used to assess mitochondrial morphology and mitophagy. Mitochondrial-related protein were confirmed with immunoblotting. Mitochondrial function was assessed with ATP measurements.
RESULTS
RESULTS
Lasmiditan treatment improved mitochondrial and kidney recovery as early as 3d post-AKI, as evidenced by increased ATP, and decreased serum creatinine, respectively. Electron micrographs of renal cortices revealed that lasmiditan also decreased mitochondrial damage and increased mitochondrial area and size by 6d after I/R injury. Additionally, lasmiditan treatment increased mitolysosomes by 3d, indicating induction of mitophagy. Phosphorylation of mitophagy-related proteins were also increased in the renal cortices of lasmiditan-treated AKI mice 3d after I/R injury, whereas fusion-related proteins were increased at 6d after I/R injury.
CONCLUSION
CONCLUSIONS
These data reveal that lasmiditan accelerates renal recovery, restores normal mitochondrial membrane and cristae morphology, decreases excessive mitochondrial fission, and accelerates mitophagy post-AKI in a time-dependent manner, establishing mitochondrial function and recovery from AKI.
Identifiants
pubmed: 37866804
pii: S0006-2952(23)00446-X
doi: 10.1016/j.bcp.2023.115855
pii:
doi:
Substances chimiques
lasmiditan
760I9WM792
Creatinine
AYI8EX34EU
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115855Subventions
Organisme : BLRD VA
ID : I01 BX000851
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.