PMID- 25271986
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 10
DP  - 2014
TI  - Gemcitabine induces poly (ADP-ribose) polymerase-1 (PARP-1) degradation through 
      autophagy in pancreatic cancer.
PG  - e109076
LID - 10.1371/journal.pone.0109076 [doi]
LID - e109076
AB  - Poly (ADP-ribose) polymerase-1 (PARP-1) and autophagy play increasingly important 
      roles in DNA damage repair and cell death. Gemcitabine (GEM) remains the 
      first-line chemotherapeutic drug for pancreatic cancer (PC). However, little is 
      known about the relationship between PARP-1 expression and autophagy in response 
      to GEM. Here we demonstrate that GEM induces DNA-damage response and degradation 
      of mono-ADP ribosylated PARP-1 through the autophagy pathway in PC cells, which 
      is rescued by inhibiting autophagy. Hypoxia and serum starvation inhibit 
      autophagic activity due to abrogated GEM-induced mono-ADP-ribosylated PARP-1 
      degradation. Activation of extracellular regulated protein kinases (ERK) induced 
      by serum starvation shows differences in intracellular localization as well as 
      modulation of autophagy and PARP-1 degradation in GEM-sensitive KLM1 and 
      -resistant KLM1-R cells. Our study has revealed a novel role of autophagy in 
      PARP-1 degradation in response to GEM, and the different impacts of MEK/ERK 
      signaling pathway on autophagy between GEM-sensitive and -resistant PC cells.
FAU - Wang, Yufeng
AU  - Wang Y
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan.
FAU - Kuramitsu, Yasuhiro
AU  - Kuramitsu Y
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan.
FAU - Tokuda, Kazuhiro
AU  - Tokuda K
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan.
FAU - Baron, Byron
AU  - Baron B
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan.
FAU - Kitagawa, Takao
AU  - Kitagawa T
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan.
FAU - Akada, Junko
AU  - Akada J
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan.
FAU - Maehara, Shin-ichiro
AU  - Maehara S
AD  - Department of Surgery and Science, Graduate School of Medical Science, Kyusyu 
      University, Fukuokashi, Fukuoka, Japan.
FAU - Maehara, Yoshihiko
AU  - Maehara Y
AD  - Department of Surgery and Science, Graduate School of Medical Science, Kyusyu 
      University, Fukuokashi, Fukuoka, Japan.
FAU - Nakamura, Kazuyuki
AU  - Nakamura K
AD  - Department of Biochemistry and Functional Proteomics, Yamaguchi University 
      Graduate School of Medicine, Ube, Yamaguchi, Japan; Centre of Clinical 
      Laboratories in Tokuyama Medical Association Hospital, Shunan, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141001
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0W860991D6 (Deoxycytidine)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Antimetabolites, Antineoplastic/*pharmacology
MH  - Autophagy/drug effects
MH  - Culture Media, Serum-Free
MH  - Deoxycytidine/*analogs & derivatives/pharmacology
MH  - Humans
MH  - Poly(ADP-ribose) Polymerases/*metabolism
MH  - Proteolysis
MH  - Gemcitabine
PMC - PMC4182782
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/10/02 06:00
MHDA- 2016/01/16 06:00
PMCR- 2014/10/01
CRDT- 2014/10/02 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2014/09/08 00:00 [accepted]
PHST- 2014/10/02 06:00 [entrez]
PHST- 2014/10/02 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - PONE-D-13-41466 [pii]
AID - 10.1371/journal.pone.0109076 [doi]
PST - epublish
SO  - PLoS One. 2014 Oct 1;9(10):e109076. doi: 10.1371/journal.pone.0109076. 
      eCollection 2014.