Saposin B-dependent Reconstitution of Arylsulfatase A Activity in Vitro and in Cell Culture Models of Metachromatic Leukodystrophy

Matzner, Ulrich; Breiden, Bernadette; Schwarzmann, Günter; Yaghootfam, Afshin; Fluharty, Arvan L.; Hasilík, Andrej; Sandhoff, Konrad; Gieselmann, Volkmar

doi:10.1074/jbc.m809457200

Cited by 18 publications

(16 citation statements)

References 38 publications

(30 reference statements)

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“…The lysosomal catabolism of membrane bound (glyco)sphingolipids such as GM1 ( 51 ), GM2 ( 52 ), sulfatide ( 53 ), sulfated gangliotriaosylceramide ( 54 ), glucosylceramide ( 55 ), and Cer ( 56 ) is strongly stimulated by anionic phospholipids. Dysfunction in the lysosomal sphingolipid digestion leads to lipid accumulation resulting in fatal lipid storage diseases ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that lipid cleaving activity of several endolysosomal hydrolases is stimulated more by PA and BMP than by PS and PI [arylsulfatase A ( 53 ), lysosomal phospholipase A2 ( 76 ), acid glucocerebrosidase ( 55 )]. Also, lipid mobilization and solubilization by Sap B are higher in liposomes containing PA than in those containing BMP at low pH ( 72 ).…”

Section: Discussionmentioning

confidence: 99%

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Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2

Oninla

Breiden

Babalola

et al. 2014

Journal of Lipid Research

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During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747–1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2

Oninla

Breiden

Babalola

et al. 2014

Journal of Lipid Research

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“…The marked rise in enzyme activity after differentiation ( Fig. 2B ) could be due to increased enzyme expression, or an increase in co-factors such as saposin B [44] during adipogenesis. In addition to sulfated CA, ARSA uses galactosylceramide sulfate as a substrate.…”

Section: Discussionmentioning

confidence: 99%

Dopamine Receptors in Human Adipocytes: Expression and Functions

et al. 2011

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IntroductionDopamine (DA) binds to five receptors (DAR), classified by their ability to increase (D1R-like) or decrease (D2R-like) cAMP. In humans, most DA circulates as dopamine sulfate (DA-S), which can be de-conjugated to bioactive DA by arylsulfatase A (ARSA). The objective was to examine expression of DAR and ARSA in human adipose tissue and determine whether DA regulates prolactin (PRL) and adipokine expression and release.MethodsDAR were analyzed by RT-PCR and Western blotting in explants, primary adipocytes and two human adipocyte cell lines, LS14 and SW872. ARSA expression and activity were determined by qPCR and enzymatic assay. PRL expression and release were determined by luciferase reporter and Nb2 bioassay. Analysis of cAMP, cGMP, leptin, adiponectin and interleukin 6 (IL-6) was done by ELISA. Activation of MAPK and PI3 kinase/Akt was determined by Western blotting.ResultsDAR are variably expressed at the mRNA and protein levels in adipose tissue and adipocytes during adipogenesis. ARSA activity in adipocyte increases after differentiation. DA at nM concentrations suppresses cAMP, stimulates cGMP, and activates MAPK in adipocytes. Acting via D2R-like receptors, DA and DA-S inhibit PRL gene expression and release. Acting via D1R/D5R receptors, DA suppresses leptin and stimulates adiponectin and IL-6 release.ConclusionsThis is the first report that human adipocytes express functional DAR and ARSA, suggesting a regulatory role for peripheral DA in adipose functions. We speculate that the propensity of some DAR-activating antipsychotics to increase weight and alter metabolic homeostasis is due, in part, to their direct action on adipose tissue.

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“…The cleavage reaction can be carried out only if the sulfatide forms a complex with SapB, which makes the hydrophobic substrate soluble (Figure 1) (29). Indeed, detergents such as sodium taurodeoxycholate, can be used instead of an activator protein in in vitro experiments (22,30,31).…”

Section: Cause Of Mld: Arsa Enzyme and Sphingolipid Activator Protein Bmentioning

confidence: 99%

Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

et al. 2020

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Saposin B-dependent Reconstitution of Arylsulfatase A Activity in Vitro and in Cell Culture Models of Metachromatic Leukodystrophy

Cited by 18 publications

References 38 publications

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2

Dopamine Receptors in Human Adipocytes: Expression and Functions

Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches

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