Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes

Moruno-Manchon, Jose F.; Uzor, Ndidi-Ese; Ambati, Chandrashekar R.; Shetty, Vivekananda; Putluri, Nagireddy; Jagannath, Chinnaswamy; McCullough, Louise D.; Tsvetkov, Andrey S.

doi:10.1038/s41419-018-0599-5

Cited by 35 publications

(37 citation statements)

References 77 publications

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“…Since neurons are highly specialized post-mitotic cells, we speculated that neuronal G4 pathways may be drastically different from G4-based mechanisms in their dividing symbiotic cells, namely in astrocytes. We first confirmed that our astrocytic cultures [38] are pure astrocytes. Astrocytes were grown in culture in DMEM + serum for 3 weeks, fixed, and stained with fluorescent phalloidin and antibodies against GFAP ( Fig.…”

supporting

confidence: 70%

“…2C and 2D). As astrocytes basally have low levels of autophagy [38,40], G4 stabilization still leads to downregulating ATG7 levels in these cells. We also looked at the levels of SQSTM1, which is commonly used as an autophagic reporter.…”

mentioning

confidence: 99%

“…Astrocytic cultures were transfected with Dendra2-LC3 and photoswitched 24 h thereafter. Co-transfection with the Sphk1 (sphingosine kinase 1) gene, a genetic enhancer of autophagy [38,41,42], was used as a positive control. The decay of "red" Dendra2 was analyzed, and the flux via autophagy was measured.…”

mentioning

confidence: 99%

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Regulation of autophagy by DNA G-quadruplexes

Lejault¹,

Moruno-Manchon²,

Vemu³

et al. 2020

Autophagy

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Guanine-rich DNA strands can form secondary structures known as Gquadruplexes (G4-DNA). G4-DNA is important for the regulation of replication and transcription. We recently showed that the expression of Atg7, a gene that is critical for macroautophagy/autophagy, is controlled by G4-DNA in neurons. We demonstrated that the transcription factor SUB1/PC4 and the G4-DNA-specific antibody HF2 bind to a putative G4-DNA motif located in the Atg7 gene. Stabilizing G4-DNA with the G4-ligand pyridostatin (PDS) downregulates Atg7 expression in neurons. Here, we further investigated how G4-DNA in the Atg7 gene is stabilized by PDS. We show that PDS can form 1:1 and 2:1 complexes with the Atg7's G4. We also demonstrate that PDS downregulates the ATG7 protein and the expression of Atg7 in astrocytes as well as in neurons. Together with our previous findings, these data establish a novel G4-DNA-associated mechanism of autophagy regulation at a transcriptional level in neurons and astrocytes.

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supporting

confidence: 70%

mentioning

confidence: 99%

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Regulation of autophagy by DNA G-quadruplexes

Lejault¹,

Moruno-Manchon²,

Vemu³

et al. 2020

Autophagy

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“…However, little is known on the possible role of macroautophagy in the immune function of astrocytes. Recent works show that this process is needed for the homeostasis maintenance upon stimulation, but depending on the type of stressor, it can also facilitate cell death and therefore brain inflammation [128][129][130] (Figure 2).…”

Section: Cma In the Adaptive Immune Responsementioning

confidence: 99%

Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

Molina

García‐Bernal

Valdor

2019

Cancers

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Glioblastoma (GB) has been shown to up-regulate autophagy with anti- or pro-oncogenic effects. Recently, our group has shown how GB cells aberrantly up-regulate chaperone-mediated autophagy (CMA) in pericytes of peritumoral areas to modulate their immune function through cell-cell interaction and in the tumor’s own benefit. Thus, to understand GB progression, the effect that GB cells could have on autophagy of immune cells that surround the tumor needs to be deeply explored. In this review, we summarize all the latest evidence of several molecular and cellular immunosuppressive mechanisms in the perivascular tumor microenvironment. This immunosuppression has been reported to facilitate GB progression and may be differently modulated by several types of autophagy as a critical point to be considered for therapeutic interventions.

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“…Furthermore, increased levels of S1P in neurons have a neuroprotective function via the induction of autophagy by benzoxazine. This neuroprotective role was neuron specific, since benzoxazine did not induce autophagy in astrocytes [188].…”

Section: Alteration In Sp1 and Cer In Neurodegenerative Diseasementioning

confidence: 91%

The role of lipids in autophagy and its implication in neurodegeneration

Hernández-Díaz¹,

Soukup²

2020

CST

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Neurodegenerative diseases are, at present, major socioeconomic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.

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Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes

Cited by 35 publications

References 77 publications

Regulation of autophagy by DNA G-quadruplexes

Regulation of autophagy by DNA G-quadruplexes

Autophagy in the Immunosuppressive Perivascular Microenvironment of Glioblastoma

The role of lipids in autophagy and its implication in neurodegeneration

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