Background: Rdh10 is a short chain dehydrogenase essential for retinoic acid biosynthesis. Results: Rdh10, a membrane-associated enzyme, localizes with lipid droplets during acyl ester biosynthesis along with cellular retinol binding-protein, type 1 and lecithin:retinol acyltransferase. Conclusion: Lipid droplets serve as a site of retinoid homeostasis. Significance: These results provide insight into lipid droplet function and retinol metabolism.
Background
Cellular retinol-binding protein, type 1 (Crbp1), chaperones retinyl ester (RE) biosynthesis catalyzed by lecithin:retinol acyltransferase (LRAT).
Methods
We monitored the subcellular loci of LRAT and Crbp1 before and during RE biosynthesis, and compared the results to diacylglycerol:acyltransferase type 2 (DGAT2) during triacylglycerol biosynthesis in three cell lines: COS7, CHO and HepG2.
Results
Before initiation of RE biosynthesis, LRAT distributed throughout the endoplasmic reticulum (ER), similar to DGAT2, and Crpb1 localized with mitochondria associated membranes (MAM), surrounded by LRAT. Upon initiating RE biosynthesis in cells transfected with low amounts of vector to simulate physiological expression levels, Crpb1 remained with MAM, and both Crbp1 and MAM re-localized with LRAT. LRAT formed rings around the growing lipid droplets. LRAT activity was higher in these rings relative to the general ER. LRAT-containing rings colocalized with the lipid-droplet surface proteins, desnutrin/adipose triglyceride lipase and perilipin 2. Colocalization with lipid droplets required the 38 N-terminal amino acid residues of LRAT, and specifically K36 and R38. Formation of rings around the growing lipid droplets did not require functional microtubules.
General significance
These data indicate a relationship between LRAT and Crbp1 during RE biosynthesis in which MAM-associated Crpb1 and LRAT colocalize, and both surround the growing RE-containing lipid droplet. The N-terminus of LRAT, especially K36 and R38, are essential to colocalization with the lipid droplet.
Rational design is essential in the synthesis of electrocatalysts for the oxygen reduction reaction (ORR). Herein, we introduced zeolitic imidazolate framework-8(ZIF-8)and polyvinyl pyrrolidone(PVP)into the electrospinning process of the polyacrylonitrile(PAN)and hemin to increase the active site loading and exposed active area of the final product with empty bead-like structures. In this method, ZIF-8 acts as a carbon skeleton to provide a rich microporous structure that can support active sites, and as a nitrogen dopant to improve nitrogen contents. PVP changes the properties of the spinning solution, adjusts the fiber morphology, and to increase the exposed area of active sites as a pore former. The obtained Fe-N-C ORR catalyst delivered a half-wave potential (E1/2) of 0.924 V in a 0.1 M KOH solution and 0.77 V in a 0.1 M HClO4 solution. A homemade zinc air battery with power density of 236 mW cm-2 demonstrated the excellent performance of the catalyst under working conditions.
Mechanisms underlying arteriovenous malformations (AVMs) are poorly understood. Using mice with endothelial cell (EC) expression of constitutively active Notch4 (Notch4*
EC
), we show decreased arteriolar tone in vivo during brain AVM initiation. Reduced vascular tone is a primary effect of Notch4*
EC
, as isolated pial arteries from asymptomatic mice exhibited reduced pressure-induced arterial tone ex vivo. The nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-
l
-arginine (L-NNA) corrected vascular tone defects in both assays. L-NNA treatment or endothelial NOS (
eNOS
) gene deletion, either globally or specifically in ECs, attenuated AVM initiation, assessed by decreased AVM diameter and delayed time to moribund. Administering nitroxide antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl also attenuated AVM initiation. Increased NOS-dependent production of hydrogen peroxide, but not NO, superoxide, or peroxynitrite was detected in isolated Notch4*
EC
brain vessels during AVM initiation. Our data suggest that eNOS is involved in Notch4*
EC
-mediated AVM formation by up-regulating hydrogen peroxide and reducing vascular tone, thereby permitting AVM initiation and progression.
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