PMID- 30402043
OWN - NLM
STAT- MEDLINE
DCOM- 20190122
LR  - 20190122
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2018
DP  - 2018
TI  - PICK1 Deficiency Induces Autophagy Dysfunction via Lysosomal Impairment and 
      Amplifies Sepsis-Induced Acute Lung Injury.
PG  - 6757368
LID - 10.1155/2018/6757368 [doi]
LID - 6757368
AB  - Sepsis is a systemic inflammatory reaction caused by infection. Multiple organ 
      failure ultimately leads to high morbidity and mortality. Unfortunately, 
      therapies against these responses have been unsuccessful due to the insufficient 
      underlying pathophysiological evidence. Protein interacting with C-kinase 1 
      (PICK1) has received considerable attention because of its important 
      physiological functions in many tissues. However, its role in sepsis-induced 
      acute lung injury (ALI) is unclear. In this study, we used cecal ligation and 
      puncture (CLP) to establish a septic model and found that decreased 
      microtubule-associated protein-1light chain 3 (LC3)-II/LC3-I in PICK1(-/-) septic 
      mice was caused by autophagy dysfunction. Consistently, the transmission electron 
      microscopy (TEM) of bone marrow-derived macrophages (BMDMs) from PICK1(-/-) mice 
      showed the accumulation of autophagosomes as well. However, more serious damage 
      was caused by PICK1 deficiency indicating that the disrupted autophagic flux was 
      harmful to sepsis-induced ALI. We also observed that it was the impaired 
      lysosomal function that mediated autophagic flux blockade, and the autophagy 
      progress was relevant to PI3K-Akt-mTOR pathway. These findings will aid in the 
      potential development of PICK1 with novel evidence of autophagy in sepsis 
      treatment and prevention.
FAU - Mo, Yunchang
AU  - Mo Y
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Lou, Yingying
AU  - Lou Y
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Zhang, Anqi
AU  - Zhang A
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Zhang, Jingjing
AU  - Zhang J
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Zhu, Congying
AU  - Zhu C
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Zheng, Bo
AU  - Zheng B
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Li, Dan
AU  - Li D
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Zhang, Mingyuan
AU  - Zhang M
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Jin, Wenjun
AU  - Jin W
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
FAU - Wang, Junlu
AU  - Wang J
AUID- ORCID: 0000-0002-7486-2207
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, China.
AD  - Department of Anesthesiology, The People's Hospital of Wencheng, Wencheng County, 
      Wenzhou City, Zhejiang Province 325300, China.
LA  - eng
PT  - Journal Article
DEP - 20181003
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Carrier Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PICk1 protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Acute Lung Injury/*etiology/*metabolism
MH  - Animals
MH  - Autophagy/genetics/*physiology
MH  - Carrier Proteins/*metabolism
MH  - Lysosomes/*metabolism/*pathology
MH  - Macrophages/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Transmission
MH  - Microscopy, Fluorescence
MH  - Nuclear Proteins/*deficiency/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Sepsis/*complications/*metabolism
PMC - PMC6192133
EDAT- 2018/11/08 06:00
MHDA- 2019/01/23 06:00
PMCR- 2018/10/03
CRDT- 2018/11/08 06:00
PHST- 2018/02/07 00:00 [received]
PHST- 2018/07/25 00:00 [revised]
PHST- 2018/08/02 00:00 [accepted]
PHST- 2018/11/08 06:00 [entrez]
PHST- 2018/11/08 06:00 [pubmed]
PHST- 2019/01/23 06:00 [medline]
PHST- 2018/10/03 00:00 [pmc-release]
AID - 10.1155/2018/6757368 [doi]
PST - epublish
SO  - Mediators Inflamm. 2018 Oct 3;2018:6757368. doi: 10.1155/2018/6757368. 
      eCollection 2018.