Evodiamine Induces Transient Receptor Potential Vanilloid-1-Mediated Protective Autophagy in U87-MG Astrocytes.
Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which results in cognitive and motor dysfunction, neurodegenerative diseases, and death. Evodiamine (Evo) is extracted from Evodia rutaecarpa Bentham, a plant widely used in Chinese herbal medicine, which possesses variable biological abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer's disease, antimetastatic, antianoxic, and antinociceptive functions. But the effect of Evo on ischemic stroke is unclear. Increasing data suggest that activation of autophagy, an adaptive response to environmental stresses, could protect neurons from ischemia-induced cell death. In this study, we found that Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased the percentage of autophagy accompanied by an increase in apoptosis, suggesting that Evo may induce calcium-mediated protective autophagy resulting from an influx of extracellular calcium. The same phenomena were also confirmed by a small interfering RNA technique to knock down the expression of TRPV1. Finally, Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1 antagonist, indicating that Evo-induced autophagy may occur through a calcium/c-Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of extracellular calcium, which led to JNK-mediated protective autophagy, and this provides a new option for ischemic stroke treatment.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Neurosurgery, Taipei City Hospital Ren-Ai Branch, Taipei, Taiwan.
Ann-Jeng
AJ
Liu
Department of Biochemistry, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
Sheng-Hao
SH
Wang
Department of Biochemistry, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Sz-Ying
SY
Hou
Department of Biochemistry, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan.
Chien-Ju
CJ
Lin
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Neurosurgery, Taipei Municipal Wan-Fang Hospital, Taipei, Taiwan.
Wen-Ta
WT
Chiu
Department of Neurosurgery, Taipei City Hospital Ren-Ai Branch, Taipei, Taiwan.
Sheng-Huang
SH
Hsiao
Department of Surgery, College of Medicine, Taipei Medical University, Taiwan ; Division of Cardiac Surgery, Cathy General Hospital, Taipei, Taiwan.
Thay-Hsiung
TH
Chen
Department of Biochemistry, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
Chwen-Ming
CM
Shih