PMID- 25070845
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20211203
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 5
DP  - 2014 Sep 1
TI  - CaMKIV-dependent preservation of mTOR expression is required for autophagy during 
      lipopolysaccharide-induced inflammation and acute kidney injury.
PG  - 2405-15
LID - 10.4049/jimmunol.1302798 [doi]
AB  - 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-3beta 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.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Zhang, Xianghong
AU  - Zhang X
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213;
FAU - Howell, Gina M
AU  - Howell GM
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213;
FAU - Guo, Lanping
AU  - Guo L
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213;
FAU - Collage, Richard D
AU  - Collage RD
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213;
FAU - Loughran, Patricia A
AU  - Loughran PA
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213; Department 
      of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15213; and.
FAU - Zuckerbraun, Brian S
AU  - Zuckerbraun BS
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213;
FAU - Rosengart, Matthew R
AU  - Rosengart MR
AD  - Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213; Department 
      of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213 
      rosengartmr@upmc.edu.
LA  - eng
GR  - R01 GM082852/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140728
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (F-Box Proteins)
RN  - 0 (F-Box-WD Repeat-Containing Protein 7)
RN  - 0 (Fbxw7 protein, mouse)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (lipopolysaccharide, Escherichia coli O111 B4)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 4)
RN  - EC 2.7.11.17 (Camk4 protein, mouse)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Acute Kidney Injury/chemically induced/genetics/*immunology/pathology
MH  - Animals
MH  - Autophagy/*drug effects/genetics/immunology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 4/genetics/*immunology
MH  - Cell Line
MH  - F-Box Proteins/genetics/immunology
MH  - F-Box-WD Repeat-Containing Protein 7
MH  - Gene Expression Regulation/*drug effects/immunology
MH  - Glycogen Synthase Kinase 3/genetics/immunology
MH  - Glycogen Synthase Kinase 3 beta
MH  - Inflammation/chemically induced/genetics/immunology
MH  - Interleukin-6/genetics/immunology
MH  - Lipopolysaccharides/*toxicity
MH  - Macrophages/*immunology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - TOR Serine-Threonine Kinases/genetics/*immunology
MH  - Ubiquitin-Protein Ligases/genetics/immunology
PMC - PMC4215705
MID - NIHMS609573
EDAT- 2014/07/30 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/09/01
CRDT- 2014/07/30 06:00
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/09/01 00:00 [pmc-release]
AID - jimmunol.1302798 [pii]
AID - 10.4049/jimmunol.1302798 [doi]
PST - ppublish
SO  - J Immunol. 2014 Sep 1;193(5):2405-15. doi: 10.4049/jimmunol.1302798. Epub 2014 
      Jul 28.