Research Paper Volume 12, Issue 21 pp 21290—21307
S-adenosylmethionine administration inhibits levodopa-induced vascular endothelial growth factor-A expression
- 1 Department of Pharmacy, Xiangya Hospital, Central South University, Hunan, China
- 2 Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Hunan, China
- 3 Department of Pathology, Xiangya Hospital, Central South University, Hunan, China
Received: May 15, 2020 Accepted: July 17, 2020 Published: November 7, 2020https://doi.org/10.18632/aging.103863
How to Cite
Copyright: © 2020 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: 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.
Results: 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.