Tyrosine hydroxylase (TH) is a rate-limiting step enzyme in the synthesis of catecholamines. Catecholamines function both as hormones and neurotransmitters in the peripheral and central nervous systems, therefore TH’s expression and enzymatic activity is tightly regulated by various mechanisms. Several post-translational modifications have been shown to regulate TH’s enzymatic activity such as phosphorylation, nitration and S-glutathionylation. Phosphorylation at the N-terminal of TH can activate its enzymatic activity while nitration and S-glutathionylation can inactivate TH. In this study, I found that TH can also be S-nitrosylated by nitric oxide (NO) at Cys279 and TH S-nitrosylation enhances its enzymatic activity both in vitro and in vivo. These results provide a novel mechanism...[ Read more ]

Tyrosine hydroxylase (TH) is a rate-limiting step enzyme in the synthesis of catecholamines. Catecholamines function both as hormones and neurotransmitters in the peripheral and central nervous systems, therefore TH’s expression and enzymatic activity is tightly regulated by various mechanisms. Several post-translational modifications have been shown to regulate TH’s enzymatic activity such as phosphorylation, nitration and S-glutathionylation. Phosphorylation at the N-terminal of TH can activate its enzymatic activity while nitration and S-glutathionylation can inactivate TH. In this study, I found that TH can also be S-nitrosylated by nitric oxide (NO) at Cys279 and TH S-nitrosylation enhances its enzymatic activity both in vitro and in vivo. These results provide a novel mechanism of how NO can modulate TH’s enzymatic activity by S-nitrosylation.

Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is an E3 ligase enzyme that targets proteins for ubiquitination, which controls various cellular processes like transmembrane receptors functioning, insulin-like growth factor signaling, viral budding and neuronal architecture via controlling the intracellular protein degradation. However, the regulation of Nedd4 itself is now poorly understood. In this study, I found that Nedd4-1 can be S-nitrosylated at Cys182. S-nitrosylation of Nedd4-1 suppresses its E3 ligase enzymatic activity and further regulates α-synuclein degradation, which is a key process for neuronal cell degeneration in mid-brain. These results show a new pathway of Nedd4 regulation, which might be a potential mechanism of α-synuclein degradation regulation.