Localization ofd-Aspartic Acid in Elongate Spermatids in Rat Testis

Sakai, Kumiko; Homma, Hiroshi; Lee, Jen Ai; Fukushima, Takeshi; Santa, Tomofumi; Tashiro, Kensuke; Iwatsubo, Takeshi; Imai, Kazuhiro

doi:10.1006/abbi.1997.0539

Cited by 94 publications

(78 citation statements)

References 39 publications

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“…Similar discrepancies have been reported elsewhere [26,27]. Approximately 30% of total Asp is in the D-form in the rat testis [3,9]. D-Asp is mainly localized in the cytoplasm of elongate spermatids, the most mature of the germ cells, and is assumed to regulate steroidogenesis as a paracrine factor in the testis [3].…”

Section: D-a~t Effect On Star Gene Expression In Rat Leydig Cellssupporting

confidence: 80%

“…Levels of this unique amino acid are transiently increased during tissue development [1,2]. We recently demonstrated that D-Asp is localized in specific cell types in developing tissues [3][4][5] and changes its localization within the organs as well as its intracellular distribution during development [6]. Our recent study also indicated that D-Asp is actually synthesized in mammalian cells [7].…”

Section: Introductionmentioning

confidence: 91%

“…D-Asp is mainly localized in the cytoplasm of elongate spermatids, the most mature of the germ cells, and is assumed to regulate steroidogenesis as a paracrine factor in the testis [3]. D-Asp is also present in other steroidogenic tissues such as the ovary, adrenal cortex and brain [1,28], where the levels of D-Asp are developmentally and spatially regulated [1,3,6]. Our results indicate that D-Asp may regulate steroid production through modulation of StAR gene expression in these steroidogenic tissues.…”

Section: D-a~t Effect On Star Gene Expression In Rat Leydig Cellsmentioning

confidence: 99%

“…In adult rat testis, approximately 30% of the total Asp content is in the D-form [3,9]. Our previous report demonstrated that D-Asp increases human chorionic gonadotropin (hCG)-induced testosterone production in purified rat Leydig cells [10].…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of steroidogenic acute regulatory protein (STAR) geneexpression by D‐aspartate in rat Leydig cells

et al. 1999

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n-aspartate and human ehorionic gonadotropin act synergistically to increase testosterone production in purified rat Leydig cells, and n-aspartate stimulates testosterone synthesis even in the absence of human chorionic gonadotropin stimulation. In addition, D-aspartate enhances steady-state cellular mRNA and protein levels of steroidogenic acute regulatory protein, which is a key regulatory factor in gonadal and adrenal steroidogenesis, n-aspartate therefore appears to increase testosterone production in rat Leydig cells by stimulating steroidogenic acute regulatory protein gene expression. To our knowledge, this is the first report demonstrating a direct effect of D-aspartate on gene expression in mammalian cells.

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Section: D-a~t Effect On Star Gene Expression In Rat Leydig Cellssupporting

confidence: 80%

Section: Introductionmentioning

confidence: 91%

Section: D-a~t Effect On Star Gene Expression In Rat Leydig Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stimulation of steroidogenic acute regulatory protein (STAR) geneexpression by D‐aspartate in rat Leydig cells

et al. 1999

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“…S3). DR and D-aspartate also are highly expressed in elongate spermatids of the testes (10,21). Besides its prominence in the developing nervous system, Daspartate is also expressed in the adult dentate gyrus.…”

Section: Resultsmentioning

confidence: 99%

Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Kim

Duan

Huang

et al. 2010

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

128

126

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D-Aspartic acid is abundant in the developing brain. We have identified and cloned mammalian aspartate racemase (DR), which converts Laspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA in newborn neurons of the adult hippocampus elicits profound defects in the dendritic development and survival of newborn neurons and survival. Because D-aspartate is a potential endogenous ligand for NMDA receptors, the loss of which elicits a phenotype resembling DR depletion, D-aspartate may function as a modulator of adult neurogenesis.neuronal development | neural progenitor cells | hippocampus | NMDA receptor | neuroendocrine D -amino acids are being increasingly recognized as putative neurotransmitters. D-serine, an endogenous ligand for the glutamate-NMDA receptor, is formed by serine racemase, a pyridoxal 5′-phosphate (PLP)-dependent enzyme that converts L-serine to D-serine (1). Deletion of serine racemase alters NMDA receptor neurotransmission and long-term potentiation (2-4), and its disturbance has been implicated in schizophrenia (5-7). D-aspartate is present in selected neuronal populations in the brain as well as in neuroendocrine tissues, such as the catecholaminergic cells of the adrenal medulla, the anterior/posterior lobes of the pituitary gland, the pineal gland, and the testes (8-10). In early neonatal stages, high D-aspartate densities in the cortical plate, subventricular zone, and discrete portions of the hippocampal formation imply a developmental role (11). In adult hippocampus, D-aspartate persists in dentate gyrus, where new neurons are generated throughout life (12, 13). These newborn neurons are integrated into existing neural circuitry and are involved in learning and memory formation (12, 13). Insight into specific neural functions for D-aspartate has been hampered by ignorance of its biosynthesis. In the present study, we identify and clone mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate. Deletion of DR leads to pronounced defects in adult hippocampal neurogenesis, implicating D-aspartate as a major regulator of neuronal development. Results and DiscussionCloning and Characterization of DR. In a genomic sequence analysis, we were unable to find candidate mammalian DR genes based on homology to serine racemase or bacterial aspartate racemases, which are either PLP-independent or PLP-dependent enzymes (14, 15). Vacca and coworkers (16-18) demonstrated that glutamate-oxalacetate transaminase (GOT) can generate small amounts of D-aspartate in the process of transaminating Laspartate to L-glutamate, and that formation of D-aspartate is augmented in GOT mutants, wherein histidine replaces tryptophan-140 and lysine replaces arginine-292. Tryptophan-140 normally prevents access of a proton donor, such as a water molecule, which can effectuate racemization (Fig. 1A); however, replacement of tryptophan-140 by histidine allows direct protonation by histidine for ...

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Organic Synthesis with Isomerases

2022

Enzyme‐Based Organic Synthesis

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Localization ofd-Aspartic Acid in Elongate Spermatids in Rat Testis

Cited by 94 publications

References 39 publications

Stimulation of steroidogenic acute regulatory protein (STAR) geneexpression by D‐aspartate in rat Leydig cells

Stimulation of steroidogenic acute regulatory protein (STAR) geneexpression by D‐aspartate in rat Leydig cells

Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis

Organic Synthesis with Isomerases

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