Mitochondrial Damage and Necroptosis in Aging Cochlea.
Aging
/ physiology
Animals
Cochlea
/ blood supply
Cytokines
/ genetics
Disease Models, Animal
Evoked Potentials, Auditory, Brain Stem
Hearing Loss, Sensorineural
/ genetics
Male
Mice, Inbred C57BL
Mitochondria
/ pathology
Necroptosis
Protein Kinases
/ genetics
Receptor-Interacting Protein Serine-Threonine Kinases
/ genetics
age-related
cochlea
hearing loss
mitochondria
necroptosis
regional blood flow
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Apr 2020
03 Apr 2020
Historique:
received:
02
03
2020
revised:
02
04
2020
accepted:
02
04
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
14
1
2021
Statut:
epublish
Résumé
Age-related hearing loss (ARHL) is an irreversible, progressive neurodegenerative disorder and is presently untreatable. Previous studies using animal models have suggested mitochondrial damage and programmed cell death to be involved with ARHL. Thus, we further investigated the pathophysiologic role of mitochondria and necroptosis in aged C57BL/6J male mice. Aged mice (20 months old) exhibited a significant loss of hearing, number of hair cells, neuronal fibers, and synaptic ribbons compared to young mice. Ultrastructural analysis of aged cochleae revealed damaged mitochondria with absent or disorganized cristae. Aged mice also showed significant decrease in cochlear blood flow, and exhibited increase in gene expression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α), receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3) and the pseudokinase mixed-lineage kinase domain-like (MLKL). Immunofluorescence (IF) assays of cytochrome C oxidase I (COX1) confirmed mitochondrial dysfunction in aged cochleae, which correlated with the degree of mitochondrial morphological damage. IF assays also revealed localization and increased expression of RIPK3 in sensorineural tissues that underwent significant necroptosis (inner and outer hair cells and stria vascularis). Together, our data shows that the aging cochlea exhibits damaged mitochondria, enhanced synthesis of proinflammatory cytokines, and provides new evidence of necroptosis in the aging cochlea in in vivo.
Identifiants
pubmed: 32260310
pii: ijms21072505
doi: 10.3390/ijms21072505
pmc: PMC7177801
pii:
doi:
Substances chimiques
Cytokines
0
MLKL protein, mouse
EC 2.7.-
Protein Kinases
EC 2.7.-
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Ripk1 protein, mouse
EC 2.7.11.1
Ripk3 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research Foundation of Korea
ID : 2018R1A2B2005022 and 2019M3E5D1A02068573
Organisme : Chungnam National University Hospital
ID : 2017-CF-030
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