PMID- 25545477
OWN - NLM
STAT- MEDLINE
DCOM- 20150501
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 95
IP  - 3
DP  - 2015 Mar
TI  - Extracellular deposition of mouse senile AApoAII amyloid fibrils induced 
      different unfolded protein responses in the liver, kidney, and heart.
PG  - 320-33
LID - 10.1038/labinvest.2014.158 [doi]
AB  - Mouse senile amyloidosis is a disorder in which apolipoprotein A-II deposits 
      extracellularly in many organs as amyloid fibrils (AApoAII). In this study, we 
      intravenously injected 1 mug of isolated AApoAII fibrils into R1.P1-Apoa2(c) mice, 
      to induce AApoAII amyloidosis. We observed that the unfolded protein response was 
      induced by deposition of AApoAII amyloid. We found that the mRNA and the protein 
      expression levels of heat shock protein A5 (HSPA5; also known as 
      glucose-regulated protein 78) were increased in the liver with AApoAII amyloid 
      deposits. Immunohistochemistry showed that HSPA5 was only detected in hepatocytes 
      close to AApoAII amyloid deposits. Furthermore, gene transcription of several 
      endoplasmic reticulum (ER) stress-related proteins increased, including 
      eukaryotic translation initiation factor 2 alpha kinase 3 (Eif2ak3), activating 
      transcription factor 6 (Atf6), activating transcription factor 4 (Atf4), 
      X-box-binding protein 1 splicing (Xbp1s), DNA-damage inducible transcript 3 
      (Ddit3), and autophagy protein 5 (Atg5). Moreover, apoptosis-positive cells were 
      increased in the liver. Similar results were seen in the kidney but not in the 
      heart. Our study indicates that ER stress responses differed among tissues with 
      extracellular AApoAII amyloid fibril deposition. Although upregulated HSPA5 and 
      the activated unfolded protein response might have roles in protecting tissues 
      against aggregated extracellular AApoAII amyloid deposition, prolonged ER stress 
      induced apoptosis in the liver and the kidney.
FAU - Luo, Hongmin
AU  - Luo H
AD  - 1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan [2] Third 
      Hospital of Hebei Medical University, Shijiazhuang, China.
FAU - Sawashita, Jinko
AU  - Sawashita J
AD  - 1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan [2] Department 
      of Biological Sciences for Intractable Neurological Diseases, Institute for 
      Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu 
      University, Matsumoto, Japan.
FAU - Tian, Geng
AU  - Tian G
AD  - 1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan [2] Shijiazhuang 
      Obstetrics and Gynecology Hospital, Shijiazhuang, China.
FAU - Liu, Yingye
AU  - Liu Y
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Li, Lin
AU  - Li L
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Ding, Xin
AU  - Ding X
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Xu, Zhe
AU  - Xu Z
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Yang, Mu
AU  - Yang M
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Miyahara, Hiroki
AU  - Miyahara H
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Mori, Masayuki
AU  - Mori M
AD  - 1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan [2] Department 
      of Advanced Medicine for Health Promotion, Institute for Biomedical Sciences, 
      Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 
      Matsumoto, Japan.
FAU - Qian, Jinze
AU  - Qian J
AD  - 1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan [2] Department 
      of Pathology, Hebei Medical University, Shijiazhuang, China.
FAU - Wang, Yaoyong
AU  - Wang Y
AD  - Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan.
FAU - Higuchi, Keiichi
AU  - Higuchi K
AD  - 1] Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, 
      Shinshu University Graduate School of Medicine, Matsumoto, Japan [2] Department 
      of Biological Sciences for Intractable Neurological Diseases, Institute for 
      Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu 
      University, Matsumoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141229
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Amyloid)
RN  - 0 (Apolipoprotein A-II)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (amyloidogenic apolipoprotein A-II, mouse)
SB  - IM
MH  - Amyloid/*metabolism
MH  - Amyloidosis/metabolism
MH  - Animals
MH  - Apolipoprotein A-II/*metabolism
MH  - Apoptosis
MH  - Blotting, Western
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress
MH  - Extracellular Space/metabolism
MH  - Gene Expression
MH  - Heat-Shock Proteins/genetics/metabolism
MH  - Hepatocytes/metabolism/pathology
MH  - Immunohistochemistry
MH  - Kidney/*metabolism
MH  - Kidney Tubules/metabolism/pathology
MH  - Liver/*metabolism
MH  - Mice
MH  - Myocardium/*metabolism
MH  - Organ Specificity
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Unfolded Protein Response
EDAT- 2014/12/30 06:00
MHDA- 2015/05/02 06:00
CRDT- 2014/12/30 06:00
PHST- 2013/12/17 00:00 [received]
PHST- 2014/09/10 00:00 [revised]
PHST- 2014/09/11 00:00 [accepted]
PHST- 2014/12/30 06:00 [entrez]
PHST- 2014/12/30 06:00 [pubmed]
PHST- 2015/05/02 06:00 [medline]
AID - S0023-6837(22)02296-6 [pii]
AID - 10.1038/labinvest.2014.158 [doi]
PST - ppublish
SO  - Lab Invest. 2015 Mar;95(3):320-33. doi: 10.1038/labinvest.2014.158. Epub 2014 Dec 
      29.