25384549 | NaDC3 Induces Premature Cellular Senescence by Promoting Transport of Krebs Cycle Intermediates, Increasing NADH, and Exacerbating Oxidative Damage |
25384549 | High-affinity sodium-dependent dicarboxylate cotransporter 3 (NaDC3) is a key metabolism-regulating membrane protein responsible for transport of Krebs cycle intermediates |
25384549 | NaDC3 is upregulated as organs age, but knowledge regarding the underlying mechanisms by which NaDC3 modulates mammalian aging is limited |
25384549 | In this study, we showed that NaDC3 overexpression accelerated cellular senescence in young human diploid cells (MRC-5 and WI-38) and primary renal tubular cells, leading to cell cycle arrest in G1 phase and increased expression of senescent biomarkers, senescence-associated beta-galactosidase and p16 |
25384549 | Stressful premature senescent phenotypes induced by NaDC3 were markedly ameliorated via treatment with the antioxidants Tiron and Tempol |
25384549 | High expression of NaDC3 caused a prominent increase in intracellular levels of Krebs cycle intermediates and NADH |
25384549 | Exogenous NADH and NAD(+) may aggravate and attenuate the aging phenotypes induced by NaDC3, respectively |
25384549 | These results suggest that NaDC3 can induce premature cellular senescence by promoting the transport of Krebs cycle intermediates, increasing generation of NADH and reactive oxygen species and leading to oxidative damage |
25384549 | Our results clarify the aging signaling pathway regulated by NaDC3 |
20813124 | High-affinity Na(+)-dependent dicarboxylate cotransporter (NaDC3) can transport Krebs cycle intermediates into cells |
20813124 | After NaDC3 was overexpressed in two human embryo lung fibroblastic cell lines, WI38 and MRC-5, we found that the cells displayed aging-related phenotypes in advance |
20813124 | In WI38/hNaDC3 cells treated with the activators of SIRT1, aging-related phenotypes induced by NaDC3 were obviously improved |
20813124 | Further study found that enhanced intracellular NAD(+) level could attenuate the aging phenotypes induced by NaDC3 |
15983172 | To investigate the role of human Na(+)/dicarboxylate cotransporter 3 (hNaDC3) in the replicative senescence of normal human embryonic lung diploid fibroblasts (WI-38), a retroviral vector containing hNaDC3 was constructed |
15983172 | Our results have, for the first time, demonstrated that high expression of hNaDC3 may be able to, at least partly, promote the cellular senescence of human diploid fibroblasts |