Elevated expression of DJ-1 (encoded by the human PARK7 gene) protects neuronal cells from sevoflurane-induced neurotoxicity

Abstract

Sevoflurane, an inhaled ether general anesthetic agent, exerts a variety of neurotoxic effects, including oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. However, the underlying molecular mechanisms remain to be elucidated. DJ-1 is a protein that exerts neuroprotective effects against different kinds of stress through multiple pathways. This study aimed to investigate the neuroprotective effects of DJ-1 against sevoflurane-induced neurotoxicity. Here, we found that sevoflurane treatment significantly increased DJ-1 expression in human neuroblastoma M17 cells in a dose-dependent manner at both the mRNA and protein levels. Interestingly, we found that overexpression of wild-type (WT) DJ-1 prevented sevoflurane-induced generation of reactive oxygen species (ROS) and nitric oxide (NO), deletion of reduced GSH, reduction of adenosine triphosphate (ATP), and mitochondrial membrane potential. Interestingly, we found that WT DJ-1 could inhibit sevoflurane-induced apoptosis by modulating the mitochondrial pathway. However, its "loss of function" mutation DJ-1(L166P) exacerbated sevoflurane-induced neurotoxicity in M17 cells. Our findings suggest that WT DJ-1 protects neuronal cells against sevoflurane-induced neurotoxicity.

Genetic variations (eQTLs) in muscle transcriptome and mitochondrial genes, and trans-eQTL molecular pathways in feed efficiency from Danish breeding pigs

“…Beyond the small gene categories from above, we also found several other interesting genes. The PARK7 gene, a gene that codes for a protein that protects from oxidative stress[ 64 ], does not appear in a pig related context in the literature, but it is found in a known FCR QTL region, and its eQTL SNP was found in a module highly correlated to FE in our previous work [ 47 ]. MFF was similarly found in a known FCR QTL region.…”

Cistanches alleviates sevoflurane‐induced cognitive dysfunction by regulating PPAR‐γ‐dependent antioxidant and anti‐inflammatory in rats

“…37,38 Moreover, an in vitro study demonstrated that inhalation of sevoflurane could increase β-AP levels and induce caspase activation and apoptosis, which can ultimately facilitate the progression of Alzheimer's disease. Studies showed that sevoflurane anaesthesia could reduce the rate of neurogenesis and decrease neuronal survival in the hippocampus, causing neurotoxicity and cognitive impairment in aged rats.…”

“…Studies showed that sevoflurane anaesthesia could reduce the rate of neurogenesis and decrease neuronal survival in the hippocampus, causing neurotoxicity and cognitive impairment in aged rats. 37,38 Moreover, an in vitro study demonstrated that inhalation of sevoflurane could increase β-AP levels and induce caspase activation and apoptosis, which can ultimately facilitate the progression of Alzheimer's disease. 39 Additionally, it is also revealed that exposure sevoflurane in aged rats led to learning and memory deficits through endoplasmic reticulum stress (ERS)-induced apoptosis of the neurons.…”

MicroRNA‐203–mediated inhibition of doublecortin underpins cardioprotection conferred by sevoflurane in rats after myocardial ischaemia‐reperfusion injury

“…3,4 Sevoflurane, an inhalational anaesthetic, has been identified to mediate multiple processes including oxidative stress, mitochondrial damage and neuronal apoptosis. 5 It has been reported that the action of SEV in myocardial I/R injury is mediated by microRNA-135b-5p. 6 This suggests that SEV may regulate other microRNAs (miRNAs) as molecular mechanisms underlying its effects against myocardial I/R injury.…”