Skip to Content
Merck
  • CaMKIV-dependent preservation of mTOR expression is required for autophagy during lipopolysaccharide-induced inflammation and acute kidney injury.

CaMKIV-dependent preservation of mTOR expression is required for autophagy during lipopolysaccharide-induced inflammation and acute kidney injury.

Journal of immunology (Baltimore, Md. : 1950) (2014-07-30)
Xianghong Zhang, Gina M Howell, Lanping Guo, Richard D Collage, Patricia A Loughran, Brian S Zuckerbraun, Matthew R Rosengart
ABSTRACT

Autophagy, an evolutionarily conserved homeostasis process regulating biomass quantity and quality, plays a critical role in the host response to sepsis. Recent studies show its calcium dependence, but the calcium-sensitive regulatory cascades have not been defined. In this study, we describe a novel mechanism in which calcium/calmodulin-dependent protein kinase IV (CaMKIV), through inhibitory serine phosphorylation of GSK-3β and inhibition of FBXW7 recruitment, prevents ubiquitin proteosomal degradation of mammalian target of rapamycin (mTOR) and thereby augments autophagy in both the macrophage and the kidney. Under the conditions of sepsis studied, mTOR expression and activity were requisite for autophagy, a paradigm countering the current perspective that prototypically, mTOR inhibition induces autophagy. CaMKIV-mTOR-dependent autophagy was fundamentally important for IL-6 production in vitro and in vivo. Similar mechanisms were operant in the kidney during endotoxemia and served a cytoprotective role in mitigating acute kidney injury. Thus, CaMKIV-mTOR-dependent autophagy is conserved in both immune and nonimmune/parenchymal cells and is fundamental for the respective functional and adaptive responses to septic insult.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetic acid-12C2, 99.9 atom % 12C
Supelco
Acetic acid, analytical standard
Sigma-Aldrich
Acetic acid, suitable for luminescence, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Acetic acid, natural, ≥99.5%, FG
Sigma-Aldrich
Acetic acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Acetic acid, glacial, ReagentPlus®, ≥99%
Sigma-Aldrich
Acetic acid, glacial, puriss., 99-100%
Sigma-Aldrich
Acetic acid, glacial, ACS reagent, ≥99.7%
Sigma-Aldrich
Acetic acid, glacial, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8%
Sigma-Aldrich
Acetic acid, glacial, ≥99.99% trace metals basis
Sigma-Aldrich
Acetic acid, glacial, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, 99.8-100.5%
Sigma-Aldrich
Acetic acid solution, suitable for HPLC
USP
Glacial acetic acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
5α-Androstan-17β-ol-3-one, purum, ≥99.0% (TLC)
Sigma-Aldrich
5α-Androstan-17β-ol-3-one, ≥97.5%
Sigma-Aldrich
Z-Leu-Leu-Leu-al, ≥90% (HPLC)
Supelco
5α-Androstan-17β-ol-3-one, VETRANAL®, analytical standard
Millipore
Bifido Selective Supplement B, suitable for microbiology