| First Author | Chleilat E | Year | 2020 |
| Journal | Int J Mol Sci | Volume | 21 |
| Issue | 8 | PubMed ID | 32326436 |
| Mgi Jnum | J:302420 | Mgi Id | MGI:6508269 |
| Doi | 10.3390/ijms21082735 | Citation | Chleilat E, et al. (2020) TGF-beta Signaling Regulates SLC8A3 Expression and Prevents Oxidative Stress in Developing Midbrain Dopaminergic and Dorsal Raphe Serotonergic Neurons. Int J Mol Sci 21(8):2735 |
| abstractText | Calcium homeostasis is a cellular process required for proper cell function and survival, maintained by the coordinated action of several transporters, among them members of the Na(+)/Ca(2+)-exchanger family, such as SLC8A3. Transforming growth factor beta (TGF-beta) signaling defines neuronal development and survival and may regulate the expression of channels and transporters. We investigated the regulation of SLC8A3 by TGF-beta in a conditional knockout mouse with deletion of TGF-beta signaling from Engrailed 1-expressing cells, i.e., in cells from the midbrain and rhombomere 1, and elucidated the underlying molecular mechanisms. The results show that SLC8A3 is significantly downregulated in developing dopaminergic and dorsal raphe serotonergic neurons in mutants and that low SLC8A3 abundance prevents the expression of the anti-apoptotic protein Bcl-xL. TGF-beta signaling affects SLC8A3 via the canonical and p38 signaling pathway and may increase the binding of Smad4 to the Slc8a3 promoter. Expression of the lipid peroxidation marker malondialdehyde (MDA) was increased following knockdown of Slc8a3 expression in vitro. In neurons lacking TGF-beta signaling, the number of MDA- and 4-hydroxynonenal (4-HNE)-positive cells was significantly increased, accompanied with increased cellular 4-HNE abundance. These results suggest that TGF-beta contributes to the regulation of SLC8A3 expression in developing dopaminergic and dorsal raphe serotonergic neurons, thereby preventing oxidative stress. |
