Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion-induced apoptosis through PI3K/Akt/GSK3β pathway in rats

Chen, Lin; Wei, Xinbing; Hou, Yingyong; Liu, Xiaoqian; Li, Senpeng; Sun, Bo; Liu, Xinyong; Liu, Huiqing

doi:10.1016/j.neuint.2014.01.006

Cited by 62 publications

(23 citation statements)

References 65 publications

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“…Further, LSZ has been proven to be an important regulator of the PI3K/AKT pathway [29,30]. Previous study reported that blocked PI3K/ AKT signaling pathway could suppress medulloblastoma growth [31].…”

Section: Discussionmentioning

confidence: 99%

Ligustrazine Inhibits Growth, Migration and Invasion of Medulloblastoma Daoy Cells by Up-Regulation of miR-211

Chi

Li³

2018

Cell Physiol Biochem

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Background/Aims: Ligustrazine (LSZ) has been identified as an antitumor agent against some types of cancers. Nevertheless, its ability to inhibit growth, migration and invasion of medulloblastoma cells is still unclear. This study aimed to explore the effect of LSZ on Daoy cells. Methods: The effects of LSZ on viability, proliferation, apoptosis, migration, and invasion of Daoy cells were analyzed by CCK-8, BrdU, flow cytometry and Transwell assays, respectively. The effect of LSZ on miR-211 expression was analyzed by qRT-PCR. miR-211 inhibitor transfection was performed to suppress miR-211 expression. The effects of LSZ on apoptosis-related factors, MMP-2, MMP-9, and Vimentin (Vim), as well as main factors of PI3K/AKT and mTOR pathways were analyzed by Western blot. Results: LSZ inhibited viability but promoted apoptosis of Daoy cells. Additionally, the proliferative, migratory and invasive abilities of Daoy cells were decreased by LSZ. Meanwhile, LSZ promoted the activations of Caspase-3 and Caspase-9, increased Bax level, decreased Bcl-2 level, as well as inhibited the expressions of MMP-2, MMP-9 and Vim. Additionally, we found that LSZ enhanced miR-211 expression and exerted its anti-medulloblastoma effect by up-regulation of miR-211. Furthermore, LSZ inhibited PI3K/AKT and mTOR signaling pathways by up-regulating miR-211. Conclusion: LSZ suppressed medulloblastoma Daoy cells by up-regulating miR-211 and further modulating the activations of PI3K/AKT and mTOR signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Ligustrazine Inhibits Growth, Migration and Invasion of Medulloblastoma Daoy Cells by Up-Regulation of miR-211

Chi

Li³

2018

Cell Physiol Biochem

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“…CXC195 are known as a TMP analog and have the antioxidant activity and anti-apoptotic effect in neuron [13,14] and HUVECs [15]. Recent studies have shown that CXC195 inhibit proliferation and inflammatory response of LPS-induced human hepatocellular carcinoma HepG2 cells [16].…”

Section: Discussionmentioning

confidence: 99%

“…CXC195 is a TMP analog showing the antioxidant activity and anti-apoptotic effect in transient focal ischemia via inhibiting NADPH Oxidase and iNOS expression [13] and regulating PI3K-AKT-GSK3b pathway [14]. In addition, CXC195 could prevent human umbilical vein endothelial cells (HUVECs) from H 2 O 2 -induced apoptosis through inhibition of the mitochondriaand caspase-dependent pathway [15].…”

Section: Introductionmentioning

confidence: 99%

IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder carcinoma T24 cells

Zeng

Peng

Chao

et al. 2015

Biochemical and Biophysical Research Communications

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“…), which also has protective effects in the CNS (Chen et al . ). Therefore, VNS‐induced neuroprotection may be associated with antioxidant and/or anti‐apoptotic mechanisms.…”

mentioning

confidence: 97%

miR‐210 mediates vagus nerve stimulation‐induced antioxidant stress and anti‐apoptosis reactions following cerebral ischemia/reperfusion injury in rats

Jiang

Tan

et al. 2015

Journal of Neurochemistry

109

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Vagus nerve stimulation (VNS) exerts neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury and modulates redox status, potentially through the activity of miR-210, an important microRNA that is regulated by hypoxia-inducible factor and Akt-dependent pathways. The aim of this study was to determine the mechanisms of VNS-and miR-210-mediated hypoxic tolerance. Male Sprague-Dawley rats were preconditioned with a miR-210 antagomir (A) or with an antagomir control (AC), followed by middle cerebral artery occlusion and VNS treatment. The animals were divided into eight groups: sham I/R, I/R, I/R+AC, I/R+A, sham I/R+VNS, I/R+VNS, I/ R+VNS+AC, and I/R+VNS+A. Activation of the endogenous cholinergic a7 nicotinic acetylcholine receptor (a7nAchR) pathway was identified using double immunofluorescence staining. miR-210 expression was measured by PCR. Behavioral outcomes, infarct volume, and neuronal apoptosis were observed at 24 h following reperfusion. Markers of oxidative stress were detected using ELISA. Rats treated with VNS showed increased miR-210 expression as well as decreased apoptosis and antioxidant stress responses compared with the I/R group; these rats also showed increased p-Akt protein expression and significantly decreased levels of cleaved caspase 3 in the ischemic penumbra, as measured by western blot and immunofluorescence analyses, respectively. Strikingly, the beneficial effects of VNS were attenuated following miR-210 knockdown. In conclusion, our results indicate that miR-210 is a potential mediator of VNS-induced neuroprotection against I/R injury. Our study highlights the neuroprotective potential of VNS, which, to date, has been largely unexplored.

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Tetramethylpyrazine analogue CXC195 protects against cerebral ischemia/reperfusion-induced apoptosis through PI3K/Akt/GSK3β pathway in rats

Cited by 62 publications

References 65 publications

Ligustrazine Inhibits Growth, Migration and Invasion of Medulloblastoma Daoy Cells by Up-Regulation of miR-211

Ligustrazine Inhibits Growth, Migration and Invasion of Medulloblastoma Daoy Cells by Up-Regulation of miR-211

IRE1α-TRAF2-ASK1 complex-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to CXC195-induced apoptosis in human bladder carcinoma T24 cells

miR‐210 mediates vagus nerve stimulation‐induced antioxidant stress and anti‐apoptosis reactions following cerebral ischemia/reperfusion injury in rats

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