FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation

Islam, Ariful; Kagawa, Yoshiteru; Miyazaki, Hirofumi; Shil, Subrata Kumar; Umaru, Banlanjo Abdulaziz; Yasumoto, Yuki; Yamamoto, Yoshiyuki; Owada, Yuji

doi:10.1007/s12035-019-1489-2

Cited by 60 publications

(55 citation statements)

References 61 publications

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“…Astroglial LD accumulation may be induced by a potentiation of glycolytic lactate production under hypoxia, which can in turn trigger FFA production from l ‐lactate and storage of excess FFAs in astroglial LDs, as discussed. Hypoxia also triggers increased ROS production (Islam et al, 2019). If the ROS production is much higher than the cellular antioxidant capacity, it can induce peroxidation of membrane lipids (also proteins and nucleic acids), particularly polyunsaturated fatty acids, both in astrocytes and neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this, cultured astrocytes with LDs were shown not only to upregulate genes to neutralize ROS but also genes involved in FFA transport and metabolism, likely promoting accumulation of LDs and β‐oxidation (Ioannou et al, 2019). Fatty acid‐binding protein 7 was recently proposed to protect isolated astrocytes exposed to a combination of chronic hypoxia and hypoglycemia from ROS toxicity by LD formation (Islam et al, 2019). Moreover, chronic hypoxia can trigger activation of the HIF‐1 and HIF‐2 pathways in astrocytes (M. Guo et al, 2019), which may activate transcription factors altering the expression pattern of proteins involved in lipid transport and lipid metabolism, favoring LD accumulation in astrocytes, as observed in other cell types (Furuta et al, 2008; Krishnan et al, 2009; Sekiya, Hiraishi, Touyama, & Sakamoto, 2008).…”

Section: Discussionmentioning

confidence: 99%

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Astrocytes in stress accumulate lipid droplets

Smolič

Tavčar

Horvat

et al. 2021

Glia

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When the brain is in a pathological state, the content of lipid droplets (LDs), the lipid storage organelles, is increased, particularly in glial cells, but rarely in neurons. The biology and mechanisms leading to LD accumulation in astrocytes, glial cells with key homeostatic functions, are poorly understood. We imaged fluorescently labeled LDs by microscopy in isolated and brain tissue rat astrocytes and in glia‐like cells in Drosophila brain to determine the (sub)cellular localization, mobility, and content of LDs under various stress conditions characteristic for brain pathologies. LDs exhibited confined mobility proximal to mitochondria and endoplasmic reticulum that was attenuated by metabolic stress and by increased intracellular Ca2+, likely to enhance the LD–organelle interaction imaged by electron microscopy. When de novo biogenesis of LDs was attenuated by inhibition of DGAT1 and DGAT2 enzymes, the astrocyte cell number was reduced by ~40%, suggesting that in astrocytes LD turnover is important for cell survival and/or proliferative cycle. Exposure to noradrenaline, a brain stress response system neuromodulator, and metabolic and hypoxic stress strongly facilitated LD accumulation in astrocytes. The observed response of stressed astrocytes may be viewed as a support for energy provision, but also to be neuroprotective against the stress‐induced lipotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Astrocytes in stress accumulate lipid droplets

Smolič

Tavčar

Horvat

et al. 2021

Glia

View full text Add to dashboard Cite

show abstract

“…These LD-laden glia upregulate genes to neutralize the peroxidated lipids generated by activated neurons. Astrocytes in particular appear to be uniquely suited for ROS management due at least in part to fatty acid binding protein 7 expression (Islam et al, 2019). Liu and colleagues first proposed this neuron-astrocyte metabolic coupling model in which neurons under stress export oxidized lipids to astrocytes as a means of neuroprotection (Meng et al, 2015;Liu et al, 2017).…”

Section: Oxidative Stressmentioning

confidence: 99%

Lipid Droplets in Neurodegenerative Disorders

et al. 2020

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Knowledge of lipid droplets (LDs) has evolved from simple depots of lipid storage to dynamic and functionally active organelles involved in a variety of cellular functions. Studies have now informed significant roles for LDs in cellular signaling, metabolic disease, and inflammation. While lipid droplet biology has been well explored in peripheral organs such as the liver and heart, LDs within the brain are relatively understudied. The presence and function of these dynamic organelles in the central nervous system has recently gained attention, especially in the context of neurodegeneration. In this review, we summarize the current understanding of LDs within the brain, with an emphasis on their relevance in neurodegenerative diseases.

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“…Furthermore, FABP7 overexpression in U87 human glioma cell line revealed higher antioxidants enzymes expression and protected against apoptosis signaling. 55 More recently, it has been shown that FABP3 is critical for a-synuclein uptake into dopaminergic neurons and enhancement of a-synuclein spreading. This protein is also essential in 1-methyl-4phenylpyridinium (MPP + )-induced morphological abnormality, mitochondrial dysfunction and neurotoxicity, suggesting that FABP3 is a potential therapeutic target in synucleinopathies.…”

Section: Discussionmentioning

confidence: 99%

Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model

2021

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Parkinson's disease (PD) is a chronic neurodegenerative disorder mainly attributed to the progressive loss of dopaminergic neurons in the substantia nigra, which leads to uncontrolled voluntary movements causing tremors, postural instability, joint stiffness, and speech and locomotion difficulties, among other symptoms. Previous studies have shown the participation of specific peptides in neurodegenerative diseases. In this context, the present work analyzed changes in the peptide profile in zebrafish brain induced to parkinsonian conditions with 6-hydroxydopamine, using isotopic labeling techniques plus mass spectrometry. These analyses allowed the relative quantitation and identification of 118 peptides. Of these, nine peptides showed significant changes, one peptide was increased and eight decreased. The most altered sequences were fragment of cytosolic and extracellular proteins related to lipid metabolism and dynamic cytoskeleton. These results open new perspectives of study about the function of peptides in PD.

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FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation

Cited by 60 publications

References 61 publications

Astrocytes in stress accumulate lipid droplets

Astrocytes in stress accumulate lipid droplets

Lipid Droplets in Neurodegenerative Disorders

Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model

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