The influence of AICAR - direct activator of AMP-activated protein kinase (AMPK) - on liver proteome in apoE-knockout mice

作者：Suski Maciej; Wisniewska Anna; Stachowicz Aneta; Olszanecki Rafal^*; Kus Katarzyna; Bialas Magdalena; Madej Jozef; Korbut Ryszard

来源：European Journal of Pharmaceutical Sciences, 2017, 104: 406-416.

DOI：10.1016/j.ejps.2017.04.021

• AMPK
• AICAR
• Mitochondria
• apoE-knockout mice
• Proteomics

There is a growing body of evidence that altered functioning of apoE may aggravate cellular energy homeostasis and stress response, leading to oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation, leading to hypercholesterolemia, dyslipidemia, liver steatosis and neurodegeneration. One of the key cellular responses to mitochondria and ER-stress related processes and cellular energy imbalance is AMP activated protein kinase (AMPK), considered as a cellular master energy sensor and critical regulator of mitochondrial homeostasis.
The aim of our study was to use differential proteomics and transcriptomics approach to elucidate the effect of direct AMPK activator AICAR on liver proteome in apoE(-/-) mice - experimental model of atherosclerosis and moderate nonalcoholic steatosis. We applied Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling and two-dimensional chromatography coupled with mass spectrometry (2DLC-MS/MS) MudPIT strategy, as well as RT-PCR to investigate the changes in mitochondrial and cytosolic proteins and transcripts expression in 6-month old AICAR-treated apoE(-/-).
AICAR elicited induction of proteins related to mitochondrial beta-oxidation, protein degradation and energy producing pathways (i.a. tricarboxylic acid cycle members and mitochondrial adenylate kinase 2). On the other hand, AICAR repressed inflammatory and pro-apoptotic markers in the apoE(-/-) mice liver, alongside reduction in several peroxisomal proteins, possibly suggesting induction of anti-oxidative pexophagy.

• 出版日期2017-6-15