Brain Arachidonic Acid Incorporation Is Decreased in Heart Fatty Acid Binding Protein Gene-Ablated Mice

Murphy, Eric J.; Owada, Yuji; Kitanaka, Noriko; Kondo, Hisatake; Glatz, Jan F. C.

doi:10.1021/bi047292r

Cited by 94 publications

(88 citation statements)

References 82 publications

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“…To confirm that these proteins constitute the endogenous repertoire of FABPs in N18TG2 cells, we performed RT-PCR analysis in N18TG2 cells and mouse brain as a control. As expected, and in accordance with previous data (44,45), FABP3, FABP5, and FABP7 were expressed in brain (Fig. 3E).…”

Section: Aea Cellular Uptake Is Rapid and Independent Of Subcellular supporting

confidence: 93%

Identification of intracellular carriers for the endocannabinoid anandamide

Kaczocha¹,

Glaser

Deutsch³

2009

Proc. Natl. Acad. Sci. U.S.A.

311

332

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The endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) is an uncharged neuromodulatory lipid that, similar to many neurotransmitters, is inactivated through its cellular uptake and subsequent catabolism. AEA is hydrolyzed by fatty acid amide hydrolase (FAAH), an enzyme localized on the endoplasmic reticulum. In contrast to most neuromodulators, the hydrophilic cytosol poses a diffusional barrier for the efficient delivery of AEA to its site of catabolism. Therefore, AEA likely traverses the cytosol with the assistance of an intracellular carrier that increases its solubility and rate of diffusion. To study this process, AEA uptake and hydrolysis were examined in COS-7 cells expressing FAAH restricted to the endoplasmic reticulum, mitochondria, or the Golgi apparatus. AEA hydrolysis was detectable at the earliest measurable time point (

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Section: Aea Cellular Uptake Is Rapid and Independent Of Subcellular supporting

confidence: 93%

Identification of intracellular carriers for the endocannabinoid anandamide

Kaczocha¹,

Glaser

Deutsch³

2009

Proc. Natl. Acad. Sci. U.S.A.

311

332

View full text Add to dashboard Cite

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“…development (Murphy et al, 2005;Motohashi et al, 2009). This opinion was also supported by our results that mFABP had a positive correlation with AA.…”

Section: Discussionmentioning

confidence: 99%

“…Certain reports have demonstrated that mice exhibited a spontaneous preference for linoleic acid (LA), but FAT/CD36-null mice did not exhibit such a preference (Laugerette et al, 2005). The incorporation of arachidonic acid (AA) in brain decreased if FABP was ablated (Murphy et al, 2005). These clues suggest the preferences of FA transporters, but direct evidence is lacking.…”

Section: Introductionmentioning

confidence: 99%

Selective transport of long-chain fatty acids by FAT/CD36 in skeletal muscle of broilers

Guo

Shu

Zhou

et al. 2013

Animal

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Fatty acid translocase (FAT/CD36) is a membrane receptor that facilitates long-chain fatty acid uptake. To investigate its role in the regulation of long-chain fatty acid composition in muscle tissue, we studied and compared FAT/CD36 gene expression in muscle tissues of commercial broiler chickens and Chinese local Silky fowls. The results from gas chromatography-mass spectrometry analysis of muscle samples demonstrated that Chinese local Silky fowls had significantly higher (P , 0.05) proportions of linoleic acid (LA) and palmitic acid, lower proportions (P , 0.05) of arachidonic acid (AA) and oleic acid than the commercial broiler chickens. The mRNA expression levels of fatty acid (FA) transporters (FA transport protein-1, membrane FA-binding protein, FAT/CD36 and caveolin-1) in the m. ipsilateral pectoralis and biceps femoris were analyzed by Q-PCR, and FAT/CD36 expression levels showed significant differences between these types of chickens (P , 0.01). Interestingly, the levels of FAT/CD36 expression are positively correlated with LA content (r 5 0.567, P , 0.01) but negatively correlated with palmitic acid content (r 5 20.568, P , 0.01). Further experiments in the stably transfected Chinese hamster oocytes cells with chicken FAT/CD36 cDNA demonstrated that overexpression of FAT/CD36 improves total FA uptake with a significant increase in the proportion of LA and AA, and a decreased proportion of palmitic acid. These results suggest that chicken FAT/CD36 may selectively transport LA and AA, which may lead to the higher LA deposition in muscle tissue.

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“…The mouse surgery and tracer infusion was performed as previously described (29,46,47 (pH 7.4) buffer containing "essentially fatty acid free" bovine serum albumin (50 mg/ml, Sigma Chemical Co., St. Louis, MO). Awake (3-4 hours post-operative) fasted, male mice (Snca +/+ or Snca -/-) were infused with 170 μCi/kg of [1-14 C]20:4n-6 into the femoral vein over 10 min at a constant rate of 30 μL/min.…”

Section: Mouse Surgery and Tracer Infusionmentioning

confidence: 99%

Acyl-CoA Synthetase Activity Links Wild-Type but Not Mutant α-Synuclein to Brain Arachidonate Metabolism

et al. 2006

Self Cite

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Because α-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of α-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca -/-mice. We measured [1-14 C]20:4n-6 incorporation and turnover kinetics in brain phospholipids using an established steady-state kinetic model. Liver was used as a negative control and no changes were observed between groups. In Snca -/-brains, there was a marked reduction in 20:4n-6-CoA mass and in microsomal acyl-CoA synthetases (Acsl) activity toward 20:4n-6. Microsomal Acsl activity was completely restored after the addition of exogenous wt mouse or human α-synuclein, but not by A30P, E46K, and A53T forms of α-synuclein. Acsl and acyl-CoA hydrolase expression was not different between groups. The incorporation and turnover of 20:4n-6 into brain phospholipid pools was markedly reduced. The dilution coefficient lambda, which indicates 20:4n-6 recycling between the acyl-CoA pool and brain phospholipids, was increased 3.3-fold, indicating more 20:4n-6 was entering the 20:4n-6-CoA pool from the plasma relative to that being recycled from the phospholipids. This is consistent with the reduction in Acsl activity observed in the Snca -/-mice. Using titration microcalorimetry, we determined that α-synuclein bound free 20:4n-6 (K d of 3.7 μM), but did not bind 20:4n-6-CoA. These data suggest α-synuclein is involved in substrate presentation to Acsl rather than product removal. In summary, our data demonstrate that α-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum localized acyl-CoA synthetase activity, although mutants forms of α-synuclein fail to restore this activity. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript α-Synuclein is a 140 amino acid soluble protein that is highly expressed in the central nervous system (1,2) and is abundant in presynaptic terminals of neurons (1,(3)(4)(5). α-Synuclein is also found in other regions of neurons, in astrocytes, and in oligodendroglia (6-11). Overexpression of and mutations in α-synuclein are associated with early onset Parkinson's disease (12)(13)(14)(15) and other neurodegenerative diseases (16)(17)(18)(19)(20). Despite this association with neurodegenerative diseases, the physiological function of this protein remains unclear.Several lines of evidence suggest that α-synuclein can influence brain lipid metabolism. It has structural similarities to class A2 apolipoproteins (21,22) and to fatty acid binding proteins (23), suggesting that α-synuclein may alter intracellular lipid trafficking, the regulation of lipid metabolism, and may act to stabilize lipid membranes. α-Synuclein binds to small phospholipid vesicles (22,24,25) and to brain vesicles (26). Consistent with this binding, the lack of α-synuclein decreases the resting/reserve pool of synaptic vesicles (27,28). Although the direct binding of fatty acids is controversial (23,29), recent studies indicate a strong potential for an important ...

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Brain Arachidonic Acid Incorporation Is Decreased in Heart Fatty Acid Binding Protein Gene-Ablated Mice

Cited by 94 publications

References 82 publications

Identification of intracellular carriers for the endocannabinoid anandamide

Identification of intracellular carriers for the endocannabinoid anandamide

Selective transport of long-chain fatty acids by FAT/CD36 in skeletal muscle of broilers

Acyl-CoA Synthetase Activity Links Wild-Type but Not Mutant α-Synuclein to Brain Arachidonate Metabolism

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