Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT

Abstract

Departmental sources Background: Ischemia-reperfusion injury is caused by a blood reperfusion injury in ischemic brain tissue, and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. MiR-122 is closely related to ischemia-reperfusion injury in the myocardium, kidney, and liver; however, the role in cerebral ischemiareperfusion injury has not been established. Material/Methods: In this study, cerebral ischemia-reperfusion injury was established in a rat model, and the control group was a sham-operated group. After ischemia-reperfusion injury for 6, 12, and 24 hours, brain tissue specimens were collected and the expression of miR-122 and DJ-1 were determined using quantitative real-time polymerase chain reaction. Flow cytometry was used to determine the reactive oxygen species (ROS) content. The modified Neurological Severity Score (mNSS) scale was used to evaluate the sensory and motor function defects of the rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and enzyme activity were determined. The rats in the cerebral ischemia-reperfusion injury model were divided into 2 groups (antagomir-NC group and antagomir miR-122 group). Brain neuron RN-c cells were divided into the following 4 groups: antagomir-NC, antagomir miR-122, pIRES2-blank, and pIRES2-DJ-1. Seventy-two hours after transfection, ischemia-reperfusion treatment was carried out and conventional cultured RN-c cells were used as the control group. Flow cytometry was used to detect apoptosis and western blot was used to detect the expression of DJ-1, PTEN, AKT, and p-AKT. Results: The expression of miR-122 increased significantly in the process of ischemia-reperfusion damage after cerebral infarction, while the expression of DJ-1 decreased significantly. Downregulation of miR-122 significantly increased the expression of DJ-1, enhanced the activity of the PTEN/PI3K/AKT pathway, reduced cell apoptosis, and alleviated cerebral ischemia-reperfusion injury. Conclusions: Inhibition of miR-122 can decrease cerebral ischemia-reperfusion injury by upregulating DJ-1-PTEN/PI3K/AKT pathway.

DJ-1: A promising therapeutic candidate for ischemia-reperfusion injury

“…Nonetheless, it is worth mentioning that confounding results have been obtained concerning the modulation of DJ-1 expression levels upon IR. Indeed, while some studies have reported an increased DJ-1 expression [ 24 , [144] , [145] , [146] ], other groups have observed no change [ 142 , 147 ] or even a decreased expression level [ 148 , 149 ]. As these discrepancies may be attributable to different models, experimental procedures, or time windows considered, more studies should be performed to elucidate whether and how DJ-1 expression is transcriptionally regulated under this condition.…”

Electroacupuncture Attenuates Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion via miR-137/NOX4 Axis

“…Evidence-Based Complementary and Alternative Medicine are important antioxidant enzymes, which can alleviate the injury caused by oxidative stress, and the levels of ROS and MDA reflect the degree of lipid peroxidation in cells and tissues [27][28][29]. e results showed that electroacupuncture could reduce the levels of ROS and MDA in serum.…”

Curcumin ameliorates ischemic stroke injury in rats by protecting the integrity of the blood‑brain barrier

“…The higher the score, the more severe the symptoms of neural power defciency. Neurological functions were evaluated 24 h, and 3 and 7 days following MCAO/R using a modified Neurological Severity Scale (mNSS), as previously described (26). This scale includes measurement of balance, reflex, sensory and motor skills.…”