Calcitriol confers neuroprotective effects in traumatic brain injury by activating Nrf2 signaling through an autophagy-mediated mechanism.
Mol Med
; 27(1): 118, 2021 09 23.
Article
in En
| MEDLINE
| ID: mdl-34556021
ABSTRACT
BACKGROUND:
The present study aimed to further explore the potential interaction between oxidative stress and autophagy in the progression of traumatic brain injury (TBI) and therapeutic mechanism of calcitriol, the active form of vitamin D (VitD).METHODS:
Neuroprotective effects of calcitriol were examined following TBI. We further evaluated the impacts of TBI and calcitriol treatment on autophagic process and nuclear factor E2-related factor 2 (Nrf2) signaling.RESULTS:
We found that treatment of calcitriol markedly ameliorated the neurological deficits and histopathological changes following TBI. The brain damage impaired autophagic flux and impeded Nrf2 signaling, the major regulator in antioxidant response, consequently leading to uncontrolled and excessive oxidative stress. Meanwhile, calcitriol promoted autophagic process and activated Nrf2 signaling as evidenced by the reduced Keap1 expression and enhanced Nrf2 translocation, thereby mitigating TBI-induced oxidative damage. In support, we further found that chloroquine (CQ) treatment abrogated calcitriol-induced autophagy and compromised Nrf2 activation with increased Keap1 accumulation and reduced expression of Nrf2-targeted genes. Additionally, both CQ treatment and Nrf2 genetic knockout abolished the protective effects of calcitriol against both TBI-induced neurological deficits and neuronal apoptosis.CONCLUSIONS:
Therefore, our work demonstrated a neuroprotective role of calcitriol in TBI by triggering Nrf2 activation, which might be mediated by autophagy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Calcitriol
/
Signal Transduction
/
NF-E2-Related Factor 2
/
Brain Injuries, Traumatic
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2021
Type:
Article
Affiliation country:
China