Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway

Xu, Lili; Wang, Liumin; Wen, Zhe; Li, Wu; Jiang, Yongjun; Yang, Lian; Xiao, Lulu; Xie, Yi; Ma, Minmin; Zhu, Wusheng; Ye, Ruidong; Liu, Xinfeng

doi:10.1152/ajpcell.00309.2015

Cited by 38 publications

(33 citation statements)

References 48 publications

(51 reference statements)

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“…Cav-1, a key protein abundant in astrocytes 21 , was implicated in several pathological processes, including apoptosis 23 , inflammation 43 , and autophagy 26 . Our study showed that PA treatment significantly reduced the protein levels of Cav-1 but not the mRNA levels in cultured hippocampal astrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Cav-1 is essential for cellular survival, and its overexpression alleviated ischemic death of cortical neurons 51 and hypoxia-mediated apoptosis of astrocytes 23 . In our present study, we found that the overexpression of Cav-1 attenuated PA-caused apoptotic death, whereas the downregulation of Cav-1 dramatically worsened it, with no effect on necrotic death.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that Cav-1 may influence fatty acid uptake by regulating surface availability of fatty acid translocase (FAT/CD36) 22 . Available evidence indicates that Cav-1 overexpression alleviates hypoxia-induced astrocyte apoptosis 23 , whereas Cav-1 knock-out (KO) enhances traumatic brain injury-induced neuroinflammation 24 . More importantly, Cav-1 can be degraded by hypoxia-induced autophagy in stromal fibroblasts 25 and non-small-cell lung cancer cells 26 .…”

Section: Introductionmentioning

confidence: 99%

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The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes

Chen

Nie

et al. 2018

Cell Death Dis

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The accumulation of palmitic acid (PA), implicated in obesity, can induce apoptotic cell death and inflammation of astrocytes. Caveolin-1 (Cav-1), an essential protein for astrocytes survival, can be degraded by autophagy, which is a double-edge sword that can either promote cell survival or cell death. The aim of this study was to delineate whether the autophagic degradation of Cav-1 is involved in PA-induced apoptosis and inflammation in hippocampal astrocytes. In this study we found that: (1) PA caused apoptotic death and inflammation by autophagic induction; (2) Cav-1 was degraded by PA-induced autophagy and PA induced autophagy in a Cav-1-independent manner; (3) the degradation of Cav-1 was responsible for PA-induced autophagy-dependent apoptotic cell death and inflammation; (4) chronic high-fat diet (HFD) induced Cav-1 degradation, apoptosis, autophagy, and inflammation in the hippocampal astrocytes of rats. Our results suggest that the autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes. Therefore, Cav-1 may be a potential therapeutic target for central nervous system injuries caused by PA accumulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes

Chen

Nie

et al. 2018

Cell Death Dis

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“…Knockdown of Cav-1 using Cav-1 small-interfering (si)RNA exacerbated astrocyte cell damage and impaired cellular glutamate uptake after oxygenglucose deprivation (OGD). In contrast, overexpression of the Cav-1 caveolin scaffolding domain peptide attenuated OGDinduced astrocyte apoptosis via ERK signaling (Xu et al, 2016), thus further demonstrating the importance of Cav-1 in BBB physiology (Gu et al, 2012;Fu et al, 2014).…”

Section: Brainmentioning

confidence: 91%

“…Within cellular components of the blood-brain barrier (BBB), Cav-1 regulates extracellular matrix proteins that include metalloproteinases (Virgintino et al, 2002) and tight junction proteins, which in turn modulate BBB physiology (Abbott et al, 2006;Gu et al, 2011;Liu et al, 2012;Lakhan et al, 2013;Zhao et al, 2014;Gurnik et al, 2016). Cav-1 has also been shown to be critical in hypoxia-induced astrocyte injury (Xu et al, 2016), which can lead to BBB damage and leakage. Knockdown of Cav-1 using Cav-1 small-interfering (si)RNA exacerbated astrocyte cell damage and impaired cellular glutamate uptake after oxygenglucose deprivation (OGD).…”

Section: Brainmentioning

confidence: 99%

Caveolins as Regulators of Stress Adaptation

2018

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Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical to life, they are central to stress adaptation in a number of organs. The following review will focus specifically on the role of caveolin in stress adaptation in the heart, brain, and eye, three organs that are susceptible to acute and chronic stress and that show as well declining function with age. In addition, we consider some novel molecular mechanisms that may account for this stress adaptation and also offer potential to drive the future of caveolin research.

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Caveolin‐1 suppresses hippocampal neuron apoptosis via the regulation of HIF1α in hypoxia in naked mole‐rats

Yang

Zhao³

et al. 2022

Cell Biology International

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Naked mole-rats (NMRs) (Heterocephalus glaber) are highly social and subterranean rodents with large communal colonies in burrows containing low oxygen levels. The inhibition of severe hypoxic conditions is of particular interest to this study. To understand the mechanisms that facilitate neuronal preservation during hypoxia, we investigated the proteins regulating hypoxia tolerance in NMR hippocampal neurons. Caveolin-1 (Cav-1), a transmembrane scaffolding protein, confers prosurvival signalling in the central nervous system. The present study aimed to investigate the role of Cav-1 in hypoxia-induced neuronal injury. Western blotting analysis and immunocytochemistry showed that Cav-1 expression was significantly upregulated in NMR hippocampal neurons under 8% O 2 conditions for 8 h. Cav-1 alleviates apoptotic neuronal death from hypoxia. Downregulation of Cav-1 by lentiviral vectors suggested damage to NMR hippocampal neurons under hypoxic conditions in vitro and in vivo. Overexpression of Cav-1 by LV-Cav-1 enhanced hypoxic tolerance of NMR hippocampal neurons in vitro and in vivo. Mechanistically, the levels of hypoxia inducible factor-1α (HIF-1α) are also increased under hypoxic conditions. After inhibiting the binding of HIF-1α to hypoxia response elements in the DNA by echinomycin, Cav-1 levels were downregulated significantly. Furthermore, chromatin immunoprecipitation assays showed the direct role of HIF1α in regulating the expression levels of Cav-1 in NMR hippocampal neurons under hypoxic conditions. These findings suggest that Cav-1 plays a critical role in modulating the apoptosis of NMR hippocampal neurons and warrant further studies targeting Cav-1 to treat hypoxia-associated brain diseases.

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Caveolin-1 is a checkpoint regulator in hypoxia-induced astrocyte apoptosis via Ras/Raf/ERK pathway

Cited by 38 publications

References 48 publications

The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes

The autophagic degradation of Cav-1 contributes to PA-induced apoptosis and inflammation of astrocytes

Caveolins as Regulators of Stress Adaptation

Caveolin‐1 suppresses hippocampal neuron apoptosis via the regulation of HIF1α in hypoxia in naked mole‐rats

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