SEPS1 Gene is Activated during Astrocyte Ischemia and Shows Prominent Antiapoptotic Effects

Fradejas, Noelia; Pastor, María Dolores; Mora-Lee, Silvia; Tranque, Pedro; Calvo, Soledad

doi:10.1007/s12031-008-9069-3

Cited by 41 publications

(34 citation statements)

References 27 publications

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“…In these experiments performed with mouse astrocyte cultures, SelS expression was either (1) abrogated by siRNA technology or (2) increased through infection with an adenoviral vector harboring the complete human SelS coding sequence (AdSelS). According to our own observations, SelS siRNA reduces SelS mRNA expression in astrocytes to less than 1% (Fradejas et al, 2008), while transduction with AdSelS sharply increases it (Fig. 6A,B).…”

Section: Sels Controls Er-stress and Inflammatory-responses In Cultursupporting

confidence: 56%

“…Even though direct evidence of SelS expression in brain astrocytes has not been obtained yet, a search for ischemia-induced genes led us to identify SelS in mouse primary astrocyte cultures (Fradejas et al, 2008). Moreover, in this study, we provided evidence that SelS supports survival of cultured astrocytes subjected to ischemia.…”

Section: Introductionmentioning

confidence: 61%

“…The effectiveness of these siRNA to suppress SelS mRNA expression was established before (Fradejas et al, 2008). siRNAs were mixed with lipofectamine 2000 (Invitrogen) according to the manufacturer's recommendations and added to the cells.…”

Section: Small Interference Rna Treatmentmentioning

confidence: 99%

“…SelS expression in astrocytes was first detected 12 h after KA treatment, and declined after 4 days. regulation (Fradejas et al, 2008). Analysis of mRNA expression by RT-PCR allowed detection of SelS in unstimulated human and mouse astrocytes, and both LPS and IL-1b triggered a significant boost in SelS mRNA (see Fig.…”

Section: Sels Expression In Human and Mouse Astrocytes Is Regulated Bmentioning

confidence: 99%

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Selenoprotein S expression in reactive astrocytes following brain injury

Fradejas

Serrano-Perez

Tranque

et al. 2011

Glia

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Selenoprotein S (SelS) is an endoplasmic reticulum (ER)-resident protein involved in the unfolded protein response. Besides reducing ER-stress, SelS attenuates inflammation by decreasing pro-inflammatory cytokines. We have recently shown that SelS is responsive to ischemia in cultured astrocytes. To check the possible association of SelS with astrocyte activation, here we investigate the expression of SelS in two models of brain injury: kainic acid (KA) induced excitotoxicity and cortical mechanical lesion. The regulation of SelS and its functional consequences for neuroinflammation, ER-stress, and cell survival were further analyzed using cultured astrocytes from mouse and human. According to our immunofluorescence analysis, SelS expression is prominent in neurons and hardly detectable in astrocytes from control mice. However, brain injury intensely upregulates SelS, specifically in reactive astrocytes. SelS induction by KA was evident at 12 h and faded out after reaching maximum levels at 3-4 days. Analysis of mRNA and protein expression in cultured astrocytes showed SelS upregulation by inflammatory stimuli as well as ER-stress inducers. In turn, siRNA-mediated SelS silencing combined with adenoviral overexpression assays demonstrated that SelS reduces ER-stress markers CHOP and spliced XBP-1, as well as inflammatory cytokines IL-1β and IL-6 in stimulated astrocytes. SelS overexpression increased astrocyte resistance to ER-stress and inflammatory stimuli. Conversely, SelS suppression compromised astrocyte viability. In summary, our results reveal the upregulation of SelS expression in reactive astrocytes, as well as a new protective role for SelS against inflammation and ER-stress that can be relevant to astrocyte function in the context of inflammatory neuropathologies.

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Section: Sels Controls Er-stress and Inflammatory-responses In Cultursupporting

confidence: 56%

Section: Introductionmentioning

confidence: 61%

Section: Small Interference Rna Treatmentmentioning

confidence: 99%

Section: Sels Expression In Human and Mouse Astrocytes Is Regulated Bmentioning

confidence: 99%

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Selenoprotein S expression in reactive astrocytes following brain injury

Fradejas

Serrano-Perez

Tranque

et al. 2011

Glia

Self Cite

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“…Furthermore, the astrocyte-targeted overexpression of superoxide dismutase 2 or heat shock protein 72 significantly reduces the loss of CA1 hippocampal neurons in a forebrain ischemia model [29]. In a recent study, Soledad Calvo et al found that inhibition of selenoprotein S1 by small interfering RNA severely increases astrocyte injury caused by OGD, suggesting that selenoprotein S protects astrocytes against ischemia [30]. Connexin43, a principal gap junction protein of astrocytes, is involved in protection from ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Liu

You²,

Tu³

et al. 2015

Cell Physiol Biochem

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Background: There is an increasing interest in the role of astrocytes contributing to the intrinsic bioremediation of ischemic brain injury. The purpose of this study was to disclose the effects and mechanism of midazolam (MDZ) on the proliferation and apoptosis of astrocytes under oxygen glucose deprivation (OGD) condition. Methods: The astrocytes were assigned randomly into four groups: control group, OGD group, OGD+MDZ group, and OGD+MDZ+IL-6 group. The astrocytes were treated with MDZ at dose of 10 μmol/L in OGD+MDZ group. And in OGD+MDZ+IL-6 group, the astrocytes were treated with MDZ at dose of 10μmol/L and IL-6 at dose of 50 ng/mL. MTT assay was used to assess cell proliferation, and cell apoptosis was analyzed by TUNEL apoptosis assay kit and flow cytometry. Furthermore, the expression of JAK2, p-JAK2, STAT3, p-STAT3, Bcl-2, Bax and Caspase-3 proteins were determined by western blotting assay. Results: Astrocytes proliferation was decreased obviously in OGD group, while MDZ could increase astrocytes proliferation under OGD condition. Moreover, OGD could induce apoptosis in astrocytes and MDZ could play an anti-apoptotic role. However, IL-6, a JAK2 activator, could attenuate cell proliferation and anti-apoptotic effects of MDZ in astrocytes. In addition, the expression of Bcl-2 protein in MDZ group increased markedly, while the JAK2/STAT3 signal proteins, Bax and Caspase-3 proteins decreased relative to OGD group. But IL-6 could counteract the anti-apoptotic effects of MDZ. Conclusion: Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. We firstly disclose the beneficial roles of midazolam in astrocytes under ischemic condition, which may be a rational treatment selection for ischemic cerebral protection.

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Selenoproteins in Cellular Redox Regulation and Signaling

Raman

Berry

2011

Oxidative Stress in Vertebrates and Invertebrates

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SEPS1 Gene is Activated during Astrocyte Ischemia and Shows Prominent Antiapoptotic Effects

Cited by 41 publications

References 27 publications

Selenoprotein S expression in reactive astrocytes following brain injury

Selenoprotein S expression in reactive astrocytes following brain injury

Midazolam Inhibits the Apoptosis of Astrocytes Induced by Oxygen Glucose Deprivation via Targeting JAK2-STAT3 Signaling Pathway

Selenoproteins in Cellular Redox Regulation and Signaling

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