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Involvement of PUMA in pericyte migration induced by methamphetamine
Yanhong Zhang1, Yuan Zhang1, Ying Bai1
1Department of Pharmacology, Medical School of Southeast University, Nanjing, China.
Experimental Cell Research
|April 15, 2017
Summary
Methamphetamine exposure increases pericyte migration by up-regulating PUMA, a protein crucial for cell movement. Targeting PUMA may offer therapies for methamphetamine-induced blood-brain barrier damage.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Methamphetamine use is linked to blood-brain barrier (BBB) damage, primarily affecting endothelial cells.
- The specific role of pericytes in methamphetamine-induced BBB dysfunction is not well understood.
- Pericytes are crucial for BBB integrity and function.
Purpose of the Study:
- To investigate the molecular mechanisms underlying methamphetamine-induced pericyte migration.
- To determine the role of PUMA (a pro-apoptotic protein) in pericyte migration.
- To explore potential therapeutic targets for mitigating methamphetamine's effects on the BBB.
Main Methods:
- Exposure of C3H/10T1/2 cells and human brain vascular pericytes (HBVPs) to methamphetamine.
- Analysis of PUMA expression and activation of sigma-1 receptor, MAPK, and Akt/PI3K pathways.
- Assessment of cell migration using in vitro assays and PUMA knockdown via siRNA.
Main Results:
- Methamphetamine exposure increased PUMA expression in pericytes through sigma-1 receptor, MAPK, and Akt/PI3K signaling.
- Methamphetamine treatment significantly enhanced pericyte migration.
- PUMA knockdown attenuated methamphetamine-induced pericyte migration by affecting integrin and tyrosine kinase pathways.
Conclusions:
- Methamphetamine-induced pericyte migration is mediated by PUMA up-regulation.
- PUMA plays a significant role in regulating pericyte migration in response to methamphetamine.
- Targeting PUMA presents a potential therapeutic strategy for addressing methamphetamine-induced BBB damage.