| First Author | Talukdar G | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1861 |
| Issue | 1 Pt A | Pages | 3378-3387 |
| PubMed ID | 27585868 | Mgi Jnum | J:251251 |
| Mgi Id | MGI:6104983 | Doi | 10.1016/j.bbagen.2016.08.020 |
| Citation | Talukdar G, et al. (2017) Novel role of serine racemase in anti-apoptosis and metabolism. Biochim Biophys Acta 1861(1 Pt A):3378-3387 |
| abstractText | BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: Because SR has two enzymatic activities, namely, racemization and alpha, beta-elimination, and SR-Q155D shows enhanced racemization and reduced alpha, beta-elimination activities, we concluded that the racemization reaction catalyzed by SR may have a more protective role against apoptosis than the alpha, beta-elimination reaction. Moreover, both of these activities are important for maximal survival and elevated levels of acetyl CoA and ATP. GENERAL SIGNIFICANCE: Our findings reveal the NMDAR-independent roles of SR in metabolism and cell survival. |
