scholarly journals Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and MPP+-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons

2019 ◽  
Vol 20 (21) ◽  
pp. 5358 ◽  
Author(s):  
Ichiro Kawahata ◽  
Luc Bousset ◽  
Ronald Melki ◽  
Kohji Fukunaga
Keyword(s):  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Dopaminergic Neurons ◽  
Fatty Acid Binding Protein ◽  
Neuronal Degeneration ◽  
Binding Protein ◽  
Mitochondrial Activity ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

α-Synuclein is an abundant neuronal protein that accumulates in insoluble inclusions in Parkinson′s disease and other synucleinopathies. Fatty acids partially regulate α-Synuclein accumulation, and mesencephalic dopaminergic neurons highly express fatty acid-binding protein 3 (FABP3). We previously demonstrated that FABP3 knockout mice show decreased α-Synuclein oligomerization and neuronal degeneration of tyrosine hydroxylase (TH)-positive neurons in vivo. In this study, we newly investigated the importance of FABP3 in α-Synuclein uptake, 1-methyl-4-phenylpyridinium (MPP+)-induced axodendritic retraction, and mitochondrial dysfunction. To disclose the issues, we employed cultured mesencephalic neurons derived from wild type or FABP3−/− C57BL6 mice and performed immunocytochemical analysis. We demonstrated that TH+ neurons from FABP3+/+ mice take up α-Synuclein monomers while FABP3−/− TH+ neurons do not. The formation of filamentous α-Synuclein inclusions following treatment with MPP+ was observed only in FABP3+/+, and not in FABP3−/− neurons. Notably, detailed morphological analysis revealed that FABP−/− neurons did not exhibit MPP+-induced axodendritic retraction. Moreover, FABP3 was also critical for MPP+-induced reduction of mitochondrial activity and the production of reactive oxygen species. These data indicate that FABP3 is critical for α-Synuclein uptake in dopaminergic neurons, thereby preventing synucleinopathies, including Parkinson′s disease.

scholarly journals Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 110
Author(s):  
Yifei Wang ◽  
Yasuharu Shinoda ◽  
An Cheng ◽  
Ichiro Kawahata ◽  
Kohji Fukunaga
Keyword(s):  
Oxidative Stress ◽  
Fatty Acid ◽  
Mitochondrial Dysfunction ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Alpha Synuclein ◽  
Fatty Acid Binding ◽  
Mitochondrial Injury ◽  
Mitochondrial Respiratory Chain Complex ◽  
Acid Binding Protein

The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co-overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.

scholarly journals Sauna dehydration as a new physiological challenge model for intestinal barrier function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Fernanda Roca Rubio ◽  
Ulrika Eriksson ◽  
Robert J. Brummer ◽  
Julia König
Keyword(s):  
Fatty Acid ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

AbstractThe intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.

scholarly journals Studies on the effect of an heterologous fatty acid-binding protein on acyl-CoA oxidase induction in Saccharomyces cerevisiae

1994 ◽  
Vol 301 (2) ◽  
pp. 615-620 ◽  
Author(s):  
I Smaczyńska ◽  
M Skoneczny ◽  
A Kurlandzka
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Yeast Cells ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Acyl Coa Oxidase

The participation of fatty acid-binding protein (FABP) in the induction of peroxisomal beta-oxidation of fatty acids was investigated in vivo in an heterologous system. Bovine heart FABP was expressed in Saccharomyces cerevisiae under the control of two different promoters: a constitutive one and an oleic acid-inducible one. Constructs were introduced into yeast cells on multicopy and integrating plasmids. The heterologous FABP was present in yeast cells in two isoforms having pI values of about 5 and was able to bind oleic acid. The heterologous FABP had no significant effect on acyl-CoA oxidase activity at various concentrations of the inducing agent.

Heart-type fatty acid-binding protein reciprocally regulates glucose and fatty acid utilization during exercise

2005 ◽  
Vol 288 (2) ◽  
pp. E292-E297 ◽  
Author(s):  
Jane Shearer ◽  
Patrick T. Fueger ◽  
Jeffrey N. Rottman ◽  
Deanna P. Bracy ◽  
Bert Binas ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Whole Body ◽  
Metabolic Clearance ◽  
Fatty Acid Binding ◽  
Nonesterified Fatty Acids ◽  
Acid Binding Protein

The role of heart-type cytosolic fatty acid-binding protein (H-FABP) in mediating whole body and muscle-specific long-chain fatty acid (LCFA) and glucose utilization was examined using exercise as a phenotyping tool. Catheters were chronically implanted in a carotid artery and jugular vein of wild-type (WT, n = 8), heterozygous (H-FABP+/−, n = 8), and null (H-FABP−/−, n = 7) chow-fed C57BL/6J mice, and mice were allowed to recover for 7 days. After a 5-h fast, conscious, unrestrained mice were studied during 30 min of treadmill exercise (0.6 mph). A bolus of [125I]-15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid and 2-deoxy-[3H]glucose was administered to obtain rates of whole body metabolic clearance (MCR) and indexes of muscle LCFA (Rf) and glucose (Rg) utilization. Fasting, nonesterified fatty acids (mM) were elevated in H-FABP−/− mice (2.2 ± 0.9 vs. 1.3 ± 0.1 and 1.3 ± 0.2 for WT and H-FABP+/−). During exercise, blood glucose (mM) increased in WT (11.7 ± 0.8) and H-FABP+/− (12.6 ± 0.9) mice, whereas H-FABP−/− mice developed overt hypoglycemia (4.8 ± 0.8). Examination of tissue-specific and whole body glucose and LCFA utilization demonstrated a dependency on H-FABP with exercise in all tissues examined. Reductions in H-FABP led to decreasing exercise-stimulated Rf and increasing Rg with the most pronounced effects in heart and soleus muscle. Similar results were seen for MCR with decreasing LCFA and increasing glucose clearance with declining levels of H-FABP. These results show that, in vivo, H-FABP has reciprocal effects on glucose and LCFA utilization and whole body fuel homeostasis when metabolic demands are elevated by exercise.

Circulating adipocyte fatty acid-binding protein induces insulin resistance in mice in vivo

Obesity ◽  
2015 ◽  
Vol 23 (5) ◽  
pp. 1007-1013 ◽  
Author(s):  
Susan Kralisch ◽  
Nora Klöting ◽  
Thomas Ebert ◽  
Matthias Kern ◽  
Annett Hoffmann ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

scholarly journals Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies

2021 ◽  
Vol 13 ◽  
Author(s):  
Hideki Oizumi ◽  
Kenshi Yamasaki ◽  
Hiroyoshi Suzuki ◽  
Takafumi Hasegawa ◽  
Yoko Sugimura ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Dopaminergic Neurons ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Amyloid Β ◽  
Human Tissues ◽  
Adult Onset ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
The Brain

Parkinson’s disease (PD) and multiple system atrophy are types of adult-onset neurodegenerative disorders named synucleinopathies, which are characterized by prominent intracellular α-synuclein (αSyn) aggregates. We have previously found that αSyn aggregates and the vulnerability of dopaminergic neurons in the mouse brain are partly associated with the expression of fatty acid-binding protein 3 (FABP3, heart FABP). However, it remains to be elucidated whether FABP3 accumulation is associated with αSyn aggregates in human tissues. Here, we histologically studied FABP3 expression in human tissues obtained from patients with synucleinopathies, patients with Alzheimer disease (AD) and controls. We found that (1) a variety of neurons expressed the FABP3 protein in human brain tissues, (2) FABP3 was colocalized with αSyn aggregates in the brains of individuals with synucleinopathies but not with amyloid β or p-tau aggregates in the brains of individuals with AD, and (3) FABP3 was not present in p-αSyn deposits in biopsied skin tissues from individuals with PD. These findings suggest that FABP3 expression is associated with αSyn aggregation in synucleinopathies and provide new insights into the involvement of FABP3 in synucleinopathies.

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