title: Novel role of serine racemase in anti-apoptosis and metabolism.
abstract: Serine racemase (SR) catalyzes the production of d-serine, a co-agonist of the N-methyl-d-aspartate receptor (NMDAR). A previous report shows the contribution of SR in the NMDAR-mediated neuronal cell death process.
  
  
  
  To analyze the intrinsic role of SR in the cell death process, we established the epithelial human embryonic kidney 293T (HEK293T) cell lines expressing wild-type SR (SR-WT), catalytically inactive mutant SR (SR-K56G), and catalytically hyperactive mutant SR (SR-Q155D). To these cell lines, staurosporine (STS), which induces apoptosis, was introduced. The cells expressing SR-WT and SR-Q155D showed resistance to STS-induced apoptosis, compared with nontransfected HEK293T cells and cells expressing SR-K56G. The SR-WT cells also showed a significant higher viability than the SR-QD cells. Furthermore, we detected elevated phosphorylation levels of Bcl-2 at serine-70 and Akt at serine-473 and threonine-308, which are related to cell survival, in the cells expressing SR-WT and SR-Q155D. From the results of metabolite analysis, we found elevated levels of acetyl CoA and ATP in cells expressing SR-WT.
  
  
  
  Because SR has two enzymatic activities, namely, racemization and α, β-elimination, and SR-Q155D shows enhanced racemization and reduced α, β-elimination activities, we concluded that the racemization reaction catalyzed by SR may have a more protective role against apoptosis than the α, β-elimination reaction. Moreover, both of these activities are important for maximal survival and elevated levels of acetyl CoA and ATP.
  
  
  
  Our findings reveal the NMDAR-independent roles of SR in metabolism and cell survival.
authors: Department of Molecular Neuroscience, Graduate School of Innovative Life Science and Medicine and Pharmaceutical Sciences, University of Toyama, Japan; Department of Biochemistry, TMSS Medical College & Hospital, Bangladesh.
authors: Gourango
authors: G
authors: Talukdar
authors: Department of Molecular Neuroscience, Graduate School of Innovative Life Science and Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors: Ran
authors: R
authors: Inoue
authors: Department of Molecular Neuroscience, Graduate School of Innovative Life Science and Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors: Tomoyuki
authors: T
authors: Yoshida
authors: Department of Molecular Neuroscience, Graduate School of Innovative Life Science and Medicine and Pharmaceutical Sciences, University of Toyama, Japan.
authors: Tetsuya
authors: T
authors: Ishimoto
authors: Frontier Research Core for Life Sciences, University of Toyama, Japan.
authors: Keisuke
authors: K
authors: Yaku
authors: Frontier Research Core for Life Sciences, University of Toyama, Japan.
authors: Takashi
authors: T
authors: Nakagawa
authors: Department of Molecular Neuroscience, Graduate School of Innovative Life Science and Medicine and Pharmaceutical Sciences, University of Toyama, Japan. Electronic address: hmori@med.u-toyama.ac.jp.
authors: Hisashi
authors: H
authors: Mori
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D012695:L-Serine Dehydratase / Q000378:metabolism; D008660:Metabolism; D055432:Metabolomics; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019998:Racemases and Epimerases / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D051025:bcl-Associated Death Protein / Q000378:metabolism; D000099300:Serine Racemase
chemical_list: D053148:Caspase 3; D045304:Cytochromes c; D012695:L-Serine Dehydratase; D011768:Pyruvate Dehydrogenase Complex; D019998:Racemases and Epimerases; D019311:Staurosporine; D051025:bcl-Associated Death Protein; D000099300:Serine Racemase
keywords: Apoptosis; NMDA receptor; Serine racemase; d-Serine