PMID- 22877754
OWN - NLM
STAT- MEDLINE
DCOM- 20121218
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 425
IP  - 2
DP  - 2012 Aug 24
TI  - IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway.
PG  - 478-84
LID - 10.1016/j.bbrc.2012.07.140 [doi]
AB  - Cellular senescence is characterized by growth arrest, enlarged and flattened 
      cell morphology, the expression of senescence-associated beta-galactosidase 
      (SA-beta-gal), and by activation of tumor suppressor networks. Insulin-like growth 
      factor-I (IGF-I) plays a critical role in cellular growth, proliferation, 
      tumorigenesis, and regulation of aging. In the present study, we show that IGF-I 
      enhances cellular senescence in mouse, rat, and human primary cells in the 
      confluent state. IGF-I induced expression of a DNA damage marker, gammaH2AX, the 
      increased levels of p53 and p21 proteins, and activated SA-beta-gal. In the 
      confluent state, an altered downstream signaling of IGF-I receptor was observed. 
      Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) 
      significantly suppressed induction of these markers, indicating that ROS are 
      involved in the induction of cellular senescence by IGF-I. In p53-null mouse 
      embryonic fibroblasts, the IGF-I-induced augmentation of SA-beta-gal and p21 was 
      inhibited, demonstrating that p53 is required for cellular senescence induced by 
      IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular 
      senescence in the ROS and p53-dependent manner and may explain the underlying 
      mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Handayaningsih, Anastasia-Evi
AU  - Handayaningsih AE
AD  - Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe 
      University Graduate School of Medicine, Kobe, Japan.
FAU - Takahashi, Michiko
AU  - Takahashi M
FAU - Fukuoka, Hidenori
AU  - Fukuoka H
FAU - Iguchi, Genzo
AU  - Iguchi G
FAU - Nishizawa, Hitoshi
AU  - Nishizawa H
FAU - Yamamoto, Masaaki
AU  - Yamamoto M
FAU - Suda, Kentaro
AU  - Suda K
FAU - Takahashi, Yutaka
AU  - Takahashi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120802
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Histones)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cellular Senescence/drug effects/*physiology
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Histones/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/pharmacology/*physiology
MH  - Mice
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Suppressor Protein p53/*metabolism
EDAT- 2012/08/11 06:00
MHDA- 2012/12/19 06:00
CRDT- 2012/08/11 06:00
PHST- 2012/07/20 00:00 [received]
PHST- 2012/07/25 00:00 [accepted]
PHST- 2012/08/11 06:00 [entrez]
PHST- 2012/08/11 06:00 [pubmed]
PHST- 2012/12/19 06:00 [medline]
AID - S0006-291X(12)01454-4 [pii]
AID - 10.1016/j.bbrc.2012.07.140 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Aug 24;425(2):478-84. doi: 
      10.1016/j.bbrc.2012.07.140. Epub 2012 Aug 2.