Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells

• 영문명: Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells
• 발행기관: 대한신경정신의학회
• 저자명: Songhee Jeon Jeong-Eun Park Young Ho Do Renata Santos Seong Mi Lee Bung-Nyun Kim Jae Hoon Cheong
• 간행물 정보: 『Psychiatry Investigation』제20권 제3호, 212~219쪽, 전체 8쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2023.03.31

영문 초록

Objective Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. Methods Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. Results Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30-60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. Conclusion These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

키워드

Atomoxetine Fluoxetine Adenosine monophosphate-activated protein kinase Carnitine palmitoyl transferase Calcium/calmodulin-dependent kinase kinase β