• Molecules and Cells
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• 제40권12호
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• pp.916-924
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• 2017

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that $Gadd45{\beta}$ (growth arrest DNA damage-inducible gene $45{\beta}$) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of $Gadd45{\beta}$. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting $Gadd45{\beta}$.

• Clinical and Experimental Pediatrics
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• 제55권7호
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• pp.238-248
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• 2012

Purpose: Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD). Methods: Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 ${\mu}M$, 10 ${\mu}M$, and 100 ${\mu}M$) on OGD-induced neurotoxicity. Results: Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 ${\mu}M$ and 100 ${\mu}M$ of L-carnitine compared with the untreated OGD group (P<0.05). The application of L-carnitine at 100 ${\mu}M$ significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P<0.05). Conclusion: L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

• 생명과학회지
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• 제19권6호
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• pp.836-838
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• 2009

뇌졸중 치료에 사용되는 tPA는 탁월한 혈전 용해 효과를 보이고 있어 혈액의 흐름을 용이하게 하는데 중요한 역할을 한다. 그러나 tPA 치료법은 매우 짧은 시간 내에 사용해야하는 단점과 출혈, 부종과 같은 여러 가지 부작용이 수반될 수 있기 때문에 매우 제한적이다. 이전의 실험 결과에 따르면 tPA의 이러한 양면적인 현상은 MMP의 활성 조절과 관련이 있는 것으로 보고되어 있으나 세포시스템을 활용한 이들의 직접적인 효과나 조절 기전에 대한 연구는 거의 알려져 있지 않다. 본 연구는 임상에서 사용되는 tPA의 부정적인 효과를 극복하기 위한 방안을 모색하고자 tPA와 MMP 활성과의 조절 기전을 살펴보았다. 랫트의 뇌로부터 추출한 신경세포에서 tPA의 처리는 MMP의 발현을 촉진시켰고 저산소상태에서 tPA에 의한 MMP활성 증가가 더욱 가속화되었으며 JNK 신호전달 경로를 통해 조절되는 것을 확인하였다.

• Journal of Preventive Medicine and Public Health
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• 제27권1호
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• pp.84-106
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• 1994

Hyperbaric oxygen (HBO) therapy for carbon monoxide (CO) poisoning eventually inducing the hypoxia-reoxygenation condition, may produce oxygen free radicals, which forms 8-hydroxydeoxyguanosine (8-OH-dG) by attacking C-8 position of deoxyguanosine (dG) in DNA. Effects of oxygen partial pressure or duration of HBO therapy with or without CO poisoning on the tissue 8-OH-dG formation were investigated. Male Sprague-Dawley rats were grouped and exposed to air (control group), 4000 ppm of CO for 10 to 30 minutes (CO only group), air for 30 minutes after 30 minute exposure to 4000 ppm of CO(CO-air exposure group), HBO after 30 minute exposure to 4000 ppm of CO(CO-HBO group), or HBO therapy fo. $10{\sim}120$ minutes(HBO only group). The 8-OH-4G concentrations in the brain and the lung tissues were measured with high performance liquid chromatography and electrochemical detector (ECD). Average concentrations of the 8-OH-dG of each group were statistically compared. In the brain tissues, 8-OH-dG concentrations of the CO only group, the CO-air exposure group, and the CO-HBO group did not significantly differ from those of the control group. Similar insignificance was also found between the CO-HBO group and the HBO only groups. No appreciable dose-response relationship was observed between the 8-OH-dG concentration and the oxygen partial pressure or the duration of HBO. However, the 8-OH-dG concentrations of the 30 minute CO only group were higher than those of the CO-air exposure group (p-value<0.05). In the lung tissues, there were no significant differences between the 8-OH-dG concentrations of the control group and those of the CO only group, the CO-air exposure group, and the CO-HBO group. However, mean 8-OH-dG concentration of the CO-air exposure group was significantly higher than that of the CO only group under the same CO exposure condition(p-value<0.05). With the duration of CO exposure, the 8-OH-dG concentrations of the lung tissues decreased significantly (p-value<0.05). The concentrations of 8-OH-dG in the lung tissues proportionally increased with the duration of HBO, but no such relation was observed with the oxygen partial pressure. These results suggest that the brain may be more resistant to oxygen free radicals as compared with the lungs, and that oxygen toxicity following HBO may be affected by factors other than oxygen free radicals.

• Journal of Ginseng Research
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• 제45권6호
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• pp.642-653
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• 2021

Background: Effective strategies are dramatically needed to prevent and improve the recovery from myocardial ischemia and reperfusion (I/R) injury. Direct interactions between the mitochondria and endoplasmic reticulum (ER) during heart diseases have been recently investigated. This study was designed to explore the cardioprotective effects of gypenoside XVII (GP-17) against I/R injury. The roles of ER stress, mitochondrial injury, and their crosstalk within I/R injury and in GP-17einduced cardioprotection are also explored. Methods: Cardiac contractility function was recorded in Langendorff-perfused rat hearts. The effects of GP-17 on mitochondrial function including mitochondrial permeability transition pore opening, reactive oxygen species production, and respiratory function were determined using fluorescence detection kits on mitochondria isolated from the rat hearts. H9c2 cardiomyocytes were used to explore the effects of GP-17 on hypoxia/reoxygenation. Results: We found that GP-17 inhibits myocardial apoptosis, reduces cardiac dysfunction, and improves contractile recovery in rat hearts. Our results also demonstrate that apoptosis induced by I/R is predominantly mediated by ER stress and associated with mitochondrial injury. Moreover, the cardioprotective effects of GP-17 are controlled by the PI3K/AKT and P38 signaling pathways. Conclusion: GP-17 inhibits I/R-induced mitochondrial injury by delaying the onset of ER stress through the PI3K/AKT and P38 signaling pathways.