Continuous administration of the mTORC1 inhibitor everolimus induces tolerance and decreases autophagy in mice.

ABSTRACT:

Background and purpose

Everolimus is an allosteric inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1) widely known for its potent autophagy stimulating properties. Because everolimus shows poor solubility and stability in aqueous solutions, long-term in vivo administration in preclinical models is challenging. The aim of the present study was to evaluate the effects of short-term and long-term everolimus administration on mTORC1 inhibition and autophagy induction in mice.

Experimental approach

We developed a vehicle in which everolimus was solubilized and stable at 37°C for at least 1 month. Using osmotic minipumps, GFP microtubule-associated protein light chain 3 transgenic mice were treated continuously either with vehicle or everolimus (1.5 mg·kg^-1</

SUBMITTER: Kurdi A 

PROVIDER: S-EPMC5738667 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature