Knockdown of Ski decreased the reactive astrocytes proliferation in vitro induced by oxygen‐glucose deprivation/reoxygenation

Zhao, Xin; Zhou, Kaisheng; Li, Zhonghao; Wu, Nan; Wang, Jing; Xia, Yayi; Zhang, Haihong

doi:10.1002/jcb.26597

Cited by 13 publications

(7 citation statements)

References 49 publications

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“…Under the paradigm of sublethal oxygen/glucose deprivation with subsequent reoxygenation, a reactive induction of astrocytic proliferation after reoxygenation is observed (38,39). The experimental conditions of this study differed in that the glucose/oxygen deprivation applied was permanent and no reoxygenation was performed to specifically measure the amount of cell death occurring under hypoxia and glucose deprivation.…”

Section: Discussionmentioning

confidence: 99%

AMPK activation protects astrocytes from hypoxia‑induced cell death

Strecker

Luger

et al. 2020

Int J Mol Med

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Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a major cellular energy sensor that is activated by an increase in the AMP/adenosine triphosphate (ATP) ratio. This causes the initiation of adaptive cellular programs, leading to the inhibition of anabolic pathways and increasing ATP synthesis. AMPK indirectly inhibits mammalian target of rapamycin (mTOR) complex 1 (mTORc1), a serine/threonine kinase and central regulator of cell growth and metabolism, which integrates various growth inhibitory signals, such as the depletion of glucose, amino acids, ATP and oxygen. While neuroprotective approaches by definition focus on neurons, that are more sensitive under cell stress conditions, astrocytes play an important role in the cerebral energy homeostasis during ischemia. Therefore, the protection of astrocytic cells or other glial cells may contribute to the preservation of neuronal integrity and function. In the present study, it was thus hypothesized that a preventive induction of energy deprivation-activated signaling pathways via AMPK may protect astrocytes from hypoxia and glucose deprivation. Hypoxia-induced cell death was measured in a paradigm of hypoxia and partial glucose deprivation in vitro in the immortalized human astrocytic cell line SVG. Both the glycolysis inhibitor 2-deoxy-d-glucose (2dG) and the AMPK activator A-769662 induced the phosphorylation of AMPK, resulting in mTORc1 inhibition, as evidenced by a decrease in the phosphorylation of the target ribosomal protein S6 (RPS6). Treatment with both 2dG and A-769662 also decreased glucose consumption and lactate production. Furthermore, A-769662, but not 2dG induced an increase in oxygen consumption, possibly indicating a more efficient glucose utilization through oxidative phosphorylation. Hypoxia-induced cell death was profoundly reduced by treatment with 2dG or A-769662. On the whole, the findings of the present study demonstrate, that AMPK activation via 2dG or A-769662 protects astrocytes under hypoxic and glucose-depleted conditions.

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Section: Discussionmentioning

confidence: 99%

AMPK activation protects astrocytes from hypoxia‑induced cell death

Strecker

Luger

et al. 2020

Int J Mol Med

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“…In addition, treatment with alpha-melanocyte-stimulating hormone [52] and caffeic acid [53] reduce infarct size and astrogliosis. Knockdown of Ski decreased the reactive astrocyte proliferation in vitro induced by oxygen-glucose deprivation/reoxygenation [54]. Thus, results from these studies suggest that stroke treatments are often accompanied by attenuating astrocyte proliferation or astrogliosis.…”

Section: Discussionmentioning

confidence: 99%

Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke

Cheng

Yeung

Zhong

et al. 2019

J Neuroinflammation

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BackgroundEndothelin-1 (ET-1) is synthesized and upregulated in astrocytes under stroke. We previously demonstrated that transgenic mice over-expressing astrocytic ET-1 (GET-1) displayed more severe neurological deficits characterized by a larger infarct after transient middle cerebral artery occlusion (tMCAO). ET-1 is a known vasoconstrictor, mitogenic, and a survival factor. However, it is unclear whether the observed severe brain damage in GET-1 mice post stroke is due to ET-1 dysregulation of neurogenesis by altering the stem cell niche.MethodsNon-transgenic (Ntg) and GET-1 mice were subjected to tMCAO with 1 h occlusion followed by long-term reperfusion (from day 1 to day 28). Neurological function was assessed using a four-point scale method. Infarct area and volume were determined by 2,3,5-triphenyltetra-zolium chloride staining. Neural stem cell (NSC) proliferation and migration in subventricular zone (SVZ) were evaluated by immunofluorescence double labeling of bromodeoxyuridine (BrdU), Ki67 and Sox2, Nestin, and Doublecortin (DCX). NSC differentiation in SVZ was evaluated using the following immunofluorescence double immunostaining: BrdU and neuron-specific nuclear protein (NeuN), BrdU and glial fibrillary acidic protein (GFAP). Phospho-Stat3 (p-Stat3) expression detected by Western-blot and immunofluorescence staining.ResultsGET-1 mice displayed a more severe neurological deficit and larger infarct area after tMCAO injury. There was a significant increase of BrdU-labeled progenitor cell proliferation, which co-expressed with GFAP, at SVZ in the ipsilateral side of the GET-1 brain at 28 days after tMCAO. p-Stat3 expression was increased in both Ntg and GET-1 mice in the ischemia brain at 7 days after tMCAO. p-Stat3 expression was significantly upregulated in the ipsilateral side in the GET-1 brain than that in the Ntg brain at 7 days after tMCAO. Furthermore, GET-1 mice treated with AG490 (a JAK2/Stat3 inhibitor) sh owed a significant reduction in neurological deficit along with reduced infarct area and dwarfed astrocytic differentiation in the ipsilateral brain after tMCAO.ConclusionsThe data indicate that astrocytic endothelin-1 overexpression promotes progenitor stem cell proliferation and astr ocytic differentiation via the Jak2/Stat3 pathway.

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“…Ski, as an evolutionary conserved protein, has been reported to exist in various tissues and species, and participates in diverse cellular processes, such as cell proliferation, metastasis, transformation and tumor progressions (6). Previous studies have demonstrated that Ski plays an essential role in certain pathophysiological processes, such as wound healing and astrocyte proliferation (15,21), vascular smooth muscle cell proliferation (22,23), muscle differentiation (24,25) and liver regeneration (26). Notably, Ski, as a novel therapeutic target, has been found over expression in the development of solid tumors (27).…”

Section: Discussionmentioning

confidence: 99%

“…The EdU reagent kit (Ribobio) was also used to evaluate cell proliferation based on our previous study (15). Briefly, the OS cells were transfected with siRNA for 48 h and the medium was then changed with culture medium to continue culture for 2 and 4 days.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway

et al. 2019

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Ski, an evolutionary conserved protein, is involved in the development of a number of tumors, such as Barrett's esophagus, leukemia, colorectal cancer, gastric cancer, pancreatic cancer, hemangiomas and melanoma. However, studies on the functions of Ski in osteosarcoma (OS) are limited. In this study, firstly the differential expression of Ski in OS tissues and osteochondroma tissues was detected, and the expression of Ski in both human OS cell lines (MG63 and U2OS) and normal osteoblasts (hFoB1.19) was then detected. The results demonstrated that Ski expression was significantly upregulated in both human OS tissues and cell lines. The results led us to hypothesize that Ski may play an essential role in the pathological process of OS. Thus, Ski specific small interfere RNA (Ski-siRNA) was used. The results revealed that OS cell proliferation was markedly inhibited following the knockdown of Ski, which was identified by CCK8 assay, EdU staining and cell cycle analysis. In addition, OS cell migration was significantly suppressed following Ski knockdown, which was identified by wound healing assay. Moreover, the protein levels of p-PI3K and p-Akt in OS cells declined prominently following Ski knockdown. On the whole, the findings of this study revealed that Ski expression was significantly upregulated in OS tissue and OS cells. The knockdown of Ski decreased OS cell proliferation and migration, which was mediated by blocking the PI3K/Akt signaling pathway. Thus, Ski may act as a tumor promoter gene in tumorigenesis, and Ski may prove to be a potential therapeutic target for the treatment of OS.

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Knockdown of Ski decreased the reactive astrocytes proliferation in vitro induced by oxygen‐glucose deprivation/reoxygenation

Cited by 13 publications

References 49 publications

AMPK activation protects astrocytes from hypoxia‑induced cell death

AMPK activation protects astrocytes from hypoxia‑induced cell death

Astrocytic endothelin-1 overexpression promotes neural progenitor cells proliferation and differentiation into astrocytes via the Jak2/Stat3 pathway after stroke

Knockdown of Ski decreases osteosarcoma cell proliferation and migration by suppressing the PI3K/Akt signaling pathway

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