S-adenosylmethionine administration inhibits levodopa-induced vascular endothelial growth factor-A expression

Studies have demonstrated that S-adenosylmethionine could effectively affect the clinical wearing-off phenomena of levodopa, an antiparkinsonian agent; however, the detailed mechanisms for this effect need to be further clarified.

These observations suggested that methyl donor S-adenosylmethionine could act as a potential agent against vascular endothelial growth factor-A-related diseases induced by levodopa treatment. Methods: We performed in vitro cytological analyses to assess whether S-adenosylmethionine intake could influence levodopa-induced vascular endothelial growth factor-A expression in human umbilical vein endothelial cells.

We performed in vitro cytological analyses to assess whether S-adenosylmethionine intake could influence levodopa-induced vascular endothelial growth factor-A expression in human umbilical vein endothelial cells.

S-adenosylmethionine and levodopa had opposite effects on the protein stability of vascular endothelial growth factor-A. The analysis of tube formation and cell viability also showed the nonconforming functions of S-adenosylmethionine and levodopa on cell angiogenesis and proliferation. Meanwhile, S-adenosylmethionine could significantly abolish the increased angiogenesis and cell viability induced by levodopa. S-adenosylmethionine resulted in G1/S phase arrest, with decreased cyclin dependent kinase 4/6 and increased p16, a specific cyclin dependent kinase inhibitor. Mechanically, the different effects of levodopa and S-adenosylmethionine were dependent on the phosphorylation and activation of extracellular signal-regulated kinase. S-adenosylmethionine could be fitted into the predicted docking pocket in the crystal structure of vascular endothelial growth factor-A, enhancing its acetylation level and reducing half-life. Conclusions: These observations suggested that methyl donor S-adenosylmethionine could act as a potential agent against vascular endothelial growth factor-A-related diseases induced by levodopa treatment. Methods: We performed in vitro cytological analyses to assess whether S-adenosylmethionine intake could influence levodopa-induced vascular endothelial growth factor-A expression in human umbilical vein endothelial cells.