Cellular studies of the two main isoforms of human d-aspartate oxidase.
cellular stability
d-aspartate
flavoproteins
neurotransmission
protein degradation
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
21
01
2021
received:
17
08
2020
accepted:
26
02
2021
pubmed:
3
3
2021
medline:
8
9
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
Human d-aspartate oxidase (hDASPO) is a FAD-dependent enzyme responsible for the degradation of d-aspartate (d-Asp). In the mammalian central nervous system, d-Asp behaves as a classical neurotransmitter, it is thought to be involved in neural development, brain morphology and behavior, and appears to be involved in several pathological states, such as schizophrenia and Alzheimer's disease. Apparently, the human DDO gene produces alternative transcripts encoding for three putative hDASPO isoforms, constituted by 341 (the 'canonical' form), 369, and 282 amino acids. Despite the increasing interest in hDASPO and its physiological role, little is known about these different isoforms. Here, the additional N-terminal peptide present in the hDASPO_369 isoform only has been identified in hippocampus of Alzheimer's disease female patients, while peptides corresponding to the remaining part of the protein were present in samples from male and female healthy controls and Alzheimer's disease patients. The hDASPO_369 isoform was largely expressed in E. coli as insoluble protein, hampering with its biochemical characterization. Furthermore, we generated U87 human glioblastoma cell clones stably expressing hDASPO_341 and, for the first time, hDASPO_369 isoforms; the latter protein showed a lower expression compared with the canonical isoform. Both protein isoforms are active (showing similar kinetic properties), localize to the peroxisomes, are very stable (a half-life of approximately 100 h has been estimated), and are primarily degraded through the ubiquitin-proteasome system. These studies shed light on the properties of hDASPO isoforms with the final aim to clarify the mechanisms controlling brain levels of the neuromodulator d-Asp.
Substances chimiques
Isoenzymes
0
D-Aspartic Acid
4SR0Q8YD1X
D-Aspartate Oxidase
EC 1.4.3.1
DDO protein, human
EC 1.4.3.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4939-4954Informations de copyright
© 2021 Federation of European Biochemical Societies.
Références
Still JL, Buell MV, Knox WE & Green DE (1949) Studies on the cyclophorase system; D-aspartic oxidase. J Biol Chem 179, 831-837.
Takahashi S (2020) D-Aspartate oxidase: distribution, functions, properties, and biotechnological applications. Appl Microbiol Biotechnol 104, 2883-2895.
Negri A, Massey V & Williams CH Jr (1987) D-aspartate oxidase from beef kidney. Purification and properties. J Biol Chem 262, 10026-10034.
Pollegioni L, Piubelli L, Sacchi S, Pilone MS & Molla G (2007) Physiological functions of D-amino acid oxidases: from yeast to humans. Cell Mol Life Sci 64, 1373-1394.
Di Fiore MM, Santillo A & Chieffi Baccari G (2014) Current knowledge of D-aspartate in glandular tissues. Amino Acids 46, 1805-1818.
Dunlop DS, Neidle A, McHale D, Dunlop DM & Lajtha A (1986) The presence of free D-aspartic acid in rodents and man. Biochem Biophys Res Commun 141, 27-32.
Hashimoto A, Kumashiro S, Nishikawa T, Oka T, Takahashi K, Mito T, Takashima S, Doi N, Mizutani Y, Yamazaki T et al. (1993) Embryonic development and postnatal changes in free D-aspartate and D-serine in the human prefrontal cortex. J Neurochem 61, 348-351.
Ota N, Shi T & Sweedler JV (2012) D-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids 43, 1873-1886.
Cristino L, Luongo L, Squillace M, Paolone G, Mango D, Piccinin S, Zianni E, Imperatore R, Iannotta M, Longo F et al. (2015) D-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain. Neurobiol Aging 36, 1890-1902.
Molinaro G, Pietracupa S, Di Menna L, Pescatori L, Usiello A, Battaglia G, Nicoletti F & Bruno V (2010) D-aspartate activates mGlu receptors coupled to polyphosphoinositide hydrolysis in neonate rat brain slices. Neurosci Lett 478, 128-130.
Errico F, Nisticò R, Napolitano F, Mazzola C, Astone D, Pisapia T, Giustizieri M, D'Aniello A, Mercuri NB & Usiello A (2011) Increased D-aspartate brain content rescues hippocampal age-related synaptic plasticity deterioration of mice. Neurobiol Aging 32, 2229-2243.
Schell MJ, Cooper OB & Snyder SH (1997) D-aspartate localizations imply neuronal and neuroendocrine roles. Proc Natl Acad Sci USA 94, 2013-2018.
Errico F, Napolitano F, Nisticò R, Centonze D & Usiello A (2009) D-aspartate: an atypical amino acid with neuromodulatory activity in mammals. Rev Neurosci 20, 429-440.
Errico F, Napolitano F, Nisticò R & Usiello A (2012) New insights on the role of free D-aspartate in the mammalian brain. Amino Acids 43, 1861-1871.
Punzo D, Errico F, Cristino L, Sacchi S, Keller S, Belardo C, Luongo L, Nuzzo T, Imperatore R, Florio E et al. (2016) Age-related changes in D-aspartate oxidase promoter methylation control extracellular D-aspartate levels and prevent precocious cell death during brain aging. J Neurosci 36, 3064-3078.
Errico F, Nisticò R, Napolitano F, Oliva AB, Romano R, Barbieri F, Florio T, Russo C, Mercuri NB & Usiello A (2011) Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay. Neurobiol Aging 32, 2061-2074.
Errico F, Nisticò R, Palma G, Federici M, Affuso A, Brilli E, Topo E, Centonze D, Bernardi G, Bozzi Y et al. (2008) Increased levels of D-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility. Mol Cell Neurosci 37, 236-246.
Molla G, Chaves-Sanjuan A, Savinelli A, Nardini M & Pollegioni L (2020) Structure and kinetic properties of human D-aspartate oxidase, the enzyme-controlling D-aspartate levels in brain. FASEB J 34, 1182-1197.
Setoyama C & Miura R (1997) Structural and functional characterization of the human brain D-aspartate oxidase. J Biochem 121, 798-803.
Sacchi S, Novellis V, Paolone G, Nuzzo T, Iannotta M, Belardo C, Squillace M, Bolognesi P, Rosini E, Motta Z et al. (2017) Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity. Sci Rep 7, 46288.
Cappelletti P, Campomenosi P, Pollegioni L & Sacchi S (2014) The degradation (by distinct pathways) of human D-amino acid oxidase and its interacting partner pLG72-two key proteins in D-serine catabolism in the brain. FEBS J 281, 708-723.
Zhao J, Zhai B, Gygi SP & Goldberg AL (2015) mTOR inhibition activates overall protein degradation by the ubiquitin proteasome system as well as by autophagy. Proc Natl Acad Sci USA 112, 15790-15797.
Ciechanover A (2005) Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6, 79-87.
Zhang T, Shen S, Qu J & Ghaemmaghami S (2016) Global analysis of cellular protein flux quantifies the selectivity of basal autophagy. Cell Rep 14, 2426-2439.
Amenta JS, Hlivko TJ, McBee AG, Shinozuka H & Brocher S (1978) Specific inhibition by NH4CL of autophagy-associated proteolysis in cultured fibroblasts. Exp Cell Res 115, 357-366.
Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ, Coppes RP, Engedal N, Mari M & Reggiori F (2018) Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy 14, 1435-1455.
Groll M & Huber R (2004) Inhibitors of the eukaryotic 20S proteasome core particle: a structural approach. Biochim Biophys Acta 1695, 33-44.
Le Bail M, Martineau M, Sacchi S, Yatsenko N, Radzishevsky I, Conrod S, Ait Ouares K, Wolosker H, Pollegioni L, Billard JM & et al. (2015) Identity of the NMDA receptor coagonist is synapse specific and developmentally regulated in the hippocampus. Proc Natl Acad Sci USA 112, E204-E213.
Pollegioni L & Sacchi S (2010) Metabolism of the neuromodulator D-serine. Cell Mol Life Sci 67, 2387-2404.
Wolosker H (2011) Serine racemase and the serine shuttle between neurons and astrocytes. Biochim Biophys Acta 1814, 1558-1566.
Sacchi S, Caldinelli L, Cappelletti P, Pollegioni L & Molla G (2012) Structure-function relationships in human D-amino acid oxidase. Amino Acids 43, 1833-1850.
Mellman WJ, Schimke RT & Hayflick L (1972) Catalase turnover in human diploid cell cultures. Exp Cell Res 73, 399-409.
Huybrechts SJ, Van Veldhoven PP, Brees C, Mannaerts GP, Los GV & Fransen M (2009) Peroxisome dynamics in cultured mammalian cells. Traffic 10, 1722-1733.
Nordgren M, Wang B, Apanasets O & Fransen M (2013) Peroxisome degradation in mammals: mechanisms of action, recent advances, and perspectives. Front Physiol 4, 145.
Léon S, Goodman JM & Subramani S (2006) Uniqueness of the mechanism of protein import into the peroxisome matrix: transport of folded, co-factor-bound and oligomeric proteins by shuttling receptors. Biochim Biophys Acta 1763, 1552-1564.
Leithe E & Rivedal E (2004) Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43. J Cell Sci 117, 1211-1220.
Katane M, Yamada S, Kawaguchi G, Chinen M, Matsumura M, Ando T, Doi I, Nakayama K, Kaneko Y, Matsuda S et al. (2015) Identification of novel D-Aspartate oxidase inhibitors by in silico screening and their functional and structural characterization in vitro. J Med Chem 58, 7328-7340.
Eberini I, Calabresi L, Wait R, Tedeschi G, Pirillo A, Puglisi L & Sirtori C (2002) Macrophage metalloproteinases degrade high-density-lipoprotein-associated apolipoprotein A-1 at both the N- and C- terminal. Biochem J 362, 627-634.
Tamplenizza M, Lenardi C, Maffioli E, Nonnis S, Negri A, Forti S, Sogne E, De Astis S, Matteoli M, Schulte C et al. (2013) Nitric oxide synthase mediates PC12 differentiation induced by the surface topography of nanostructured TiO2. J Nanobiotec 35, 1477-3155.
Tedeschi G, Albani E, Borroni EM, Parini V, Brucculeri AM, Maffioli E, Negri A, Nonnis S, Maccarrone M & Levi-Setti PE (2017) Proteomic profile of maternal-aged blastocoel fluid suggests a novel role for ubiquitin system in blastocyst quality. J Assist Reprod Genet 34 , 225-238.