PMID- 28447205
OWN - NLM
STAT- MEDLINE
DCOM- 20180507
LR  - 20181113
IS  - 1432-1750 (Electronic)
IS  - 0341-2040 (Print)
IS  - 0341-2040 (Linking)
VI  - 195
IP  - 4
DP  - 2017 Aug
TI  - Treatment with Geranylgeranylacetone Induces Heat Shock Protein 70 and Attenuates 
      Neonatal Hyperoxic Lung Injury in a Model of Bronchopulmonary Dysplasia.
PG  - 469-476
LID - 10.1007/s00408-017-0007-4 [doi]
AB  - PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory complication 
      characterized by abnormal alveolar development in premature infants. 
      Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has 
      cytoprotective effects against various stressors. Here, we investigated whether 
      GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and 
      measured the serum HSP70 levels in preterm humans treated with oxygen. METHODS: 
      Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone 
      orally on days 1, 2, and 3 of life. At 2 days of age, HSP70 expression in the 
      lung was determined by western blotting. At 8 days of age, the lungs were 
      processed for histological analysis. Radial alveolar count (RAC) and mean linear 
      intercept (MLI) were measured as parameters of alveolarization. Apoptosis was 
      evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) method and cleaved caspase-3 immunohistochemistry. Serum HSP70 
      levels in preterm humans treated with oxygen were measured by enzyme-linked 
      immunosorbent assay. RESULTS: GGA administration enhanced the HSP70 expression to 
      two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia 
      reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed 
      mice exhibited more apoptotic cells in lung parenchyma and a more simplified 
      alveolar structure with less RAC and larger MLI than normoxia-exposed mice. GGA 
      suppressed the increase in apoptotic cells and the structural changes of the 
      lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually 
      decreased with age. CONCLUSIONS: GGA may attenuate hyperoxic injury in neonatal 
      lungs and thereby may prevent the development of BPD.
FAU - Tokuriki, Shuko
AU  - Tokuriki S
AD  - Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 
      Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan. 
      shu@u-fukui.ac.jp.
FAU - Igarashi, Aiko
AU  - Igarashi A
AD  - Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 
      Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
FAU - Okuno, Takashi
AU  - Okuno T
AD  - Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 
      Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
FAU - Ohta, Genrei
AU  - Ohta G
AD  - Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 
      Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
FAU - Naiki, Hironobu
AU  - Naiki H
AD  - Department of Pathological Sciences, Faculty of Medical Sciences, University of 
      Fukui, 23-3 Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, 
      Japan.
FAU - Ohshima, Yusei
AU  - Ohshima Y
AD  - Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 
      Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170426
PL  - United States
TA  - Lung
JT  - Lung
JID - 7701875
RN  - 0 (Diterpenes)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - S8S8451A4O (geranylgeranylacetone)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Bronchopulmonary Dysplasia/metabolism/physiopathology/*prevention & control
MH  - Cytoprotection
MH  - Disease Models, Animal
MH  - Diterpenes/*pharmacology
MH  - Failure to Thrive/etiology/physiopathology/prevention & control
MH  - Gestational Age
MH  - HSP70 Heat-Shock Proteins/blood/*metabolism
MH  - Humans
MH  - Hyperoxia/*complications/metabolism/physiopathology
MH  - Infant, Premature
MH  - Lung/*drug effects/metabolism/physiopathology
MH  - Lung Injury/etiology/metabolism/physiopathology/*prevention & control
MH  - Mice, Inbred C57BL
MH  - Oxygen Inhalation Therapy/adverse effects
MH  - Up-Regulation
PMC - PMC5522658
OTO - NOTNLM
OT  - Alveolarization
OT  - Bronchopulmonary dysplasia
OT  - Geranylgeranylacetone
OT  - Hyperoxia
COIS- CONFLICT OF INTEREST: The authors declare that they have no conflict of interest. 
      ETHICAL APPROVAL: All procedures performed in studies involving animals were in 
      accordance with the ethical standards of the institution or practice at which the 
      studies were conducted. ETHICAL STANDARDS: All procedures performed in studies 
      involving human participants were in accordance with the ethical standards of the 
      institutional research committee and with the 1964 Helsinki declaration and its 
      later amendments or comparable ethical standards. INFORMED CONSENT: The parents 
      of the infants provided written consent.
EDAT- 2017/04/28 06:00
MHDA- 2018/05/08 06:00
PMCR- 2017/04/26
CRDT- 2017/04/28 06:00
PHST- 2017/02/13 00:00 [received]
PHST- 2017/04/17 00:00 [accepted]
PHST- 2017/04/28 06:00 [pubmed]
PHST- 2018/05/08 06:00 [medline]
PHST- 2017/04/28 06:00 [entrez]
PHST- 2017/04/26 00:00 [pmc-release]
AID - 10.1007/s00408-017-0007-4 [pii]
AID - 7 [pii]
AID - 10.1007/s00408-017-0007-4 [doi]
PST - ppublish
SO  - Lung. 2017 Aug;195(4):469-476. doi: 10.1007/s00408-017-0007-4. Epub 2017 Apr 26.