PMID- 19341793
OWN - NLM
STAT- MEDLINE
DCOM- 20090917
LR  - 20211020
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Print)
IS  - 0891-5849 (Linking)
VI  - 46
IP  - 12
DP  - 2009 Jun 15
TI  - Overexpression of catalase delays G0/G1- to S-phase transition during cell cycle 
      progression in mouse aortic endothelial cells.
PG  - 1658-67
LID - 10.1016/j.freeradbiomed.2009.03.018 [doi]
AB  - Although it is understood that hydrogen peroxide (H(2)O(2)) promotes cellular 
      proliferation, little is known about its role in endothelial cell cycle 
      progression. To assess the regulatory role of endogenously produced H(2)O(2) in 
      cell cycle progression, we studied the cell cycle progression in mouse aortic 
      endothelial cells (MAECs) obtained from mice overexpressing a human catalase 
      transgene (hCatTg), which destroys H(2)O(2). The hCatTg MAECs displayed a 
      prolonged doubling time compared to wild-type controls (44.0 +/- 4.7 h versus 
      28.6 +/- 0.8 h, p<0.05), consistent with a diminished growth rate and H(2)O(2) 
      release. Incubation with aminotriazole, a catalase inhibitor, prevented the 
      observed diminished growth rate in hCatTg MAECs. Inhibition of catalase activity 
      with aminotriazole abrogated catalase overexpression-induced antiproliferative 
      action. Flow cytometry analysis indicated that the prolonged doubling time was 
      principally due to an extended G(0)/G(1) phase in hCatTg MAECs compared to the 
      wild-type cells (25.0 +/- 0.9 h versus 15.9 +/- 1.4 h, p< 0.05). The hCatTg MAECs 
      also exhibited decreased activities of the cyclin-dependent kinase (Cdk) 
      complexes responsible for G(0)/G(1)- to S-phase transition in the cell cycle, 
      including the cyclin D-Cdk4 and cyclin E-Cdk2 complexes. Moreover, the reduction 
      in cyclin-Cdk activities in hCatTg MAECs was accompanied by increased protein 
      levels of two Cdk inhibitors, p21 and p27, which inhibit the Cdk activity 
      required for the G(0)/G(1)- to S-phase transition. Knockdown of p21 and/or p27 
      attenuated the antiproliferative effect of catalase overexpression in MAECs. 
      These results, together with the fact that catalase is an H(2)O(2) scavenger, 
      suggest that endogenously produced H(2)O(2) mediates MAEC proliferation by 
      fostering the transition from G(0)/G(1) to S phase.
FAU - Onumah, Ogbeyalu E
AU  - Onumah OE
AD  - Department of Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
FAU - Jules, George E
AU  - Jules GE
FAU - Zhao, Yanfeng
AU  - Zhao Y
FAU - Zhou, LiChun
AU  - Zhou L
FAU - Yang, Hong
AU  - Yang H
FAU - Guo, ZhongMao
AU  - Guo Z
LA  - eng
GR  - K01HL-076623/HL/NHLBI NIH HHS/United States
GR  - T32HL07735/HL/NHLBI NIH HHS/United States
GR  - U54 CA091408/CA/NCI NIH HHS/United States
GR  - F31 HL083921/HL/NHLBI NIH HHS/United States
GR  - K01 HL076623-04/HL/NHLBI NIH HHS/United States
GR  - G12RR03032/RR/NCRR NIH HHS/United States
GR  - F31HL083921/HL/NHLBI NIH HHS/United States
GR  - K01 HL076623-05/HL/NHLBI NIH HHS/United States
GR  - T32 HL007735/HL/NHLBI NIH HHS/United States
GR  - 5U54CA091408-07/CA/NCI NIH HHS/United States
GR  - G12 RR003032/RR/NCRR NIH HHS/United States
GR  - R01 ES014472/ES/NIEHS NIH HHS/United States
GR  - R01ES014471/ES/NIEHS NIH HHS/United States
GR  - K01 HL076623/HL/NHLBI NIH HHS/United States
GR  - G12RR003032/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090331
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Free Radical Scavengers)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - ZF80H5GXUF (Amitrole)
SB  - IM
MH  - Amitrole/pharmacology
MH  - Animals
MH  - Aorta/*cytology
MH  - Catalase/antagonists & inhibitors/*genetics/*metabolism
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Cyclin-Dependent Kinases/antagonists & inhibitors/metabolism
MH  - Endothelium, Vascular/*cytology/drug effects/metabolism
MH  - Flow Cytometry
MH  - Free Radical Scavengers/antagonists & inhibitors/metabolism
MH  - *G1 Phase/drug effects
MH  - Gene Expression
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *Resting Phase, Cell Cycle/drug effects
MH  - *S Phase/drug effects
MH  - Signal Transduction/drug effects
PMC - PMC2713001
MID - NIHMS106600
COIS- Conflict of Interests: The authors have no conflicts to disclose.
EDAT- 2009/04/04 09:00
MHDA- 2009/09/18 06:00
PMCR- 2010/06/15
CRDT- 2009/04/04 09:00
PHST- 2008/09/12 00:00 [received]
PHST- 2009/03/23 00:00 [revised]
PHST- 2009/03/25 00:00 [accepted]
PHST- 2009/04/04 09:00 [entrez]
PHST- 2009/04/04 09:00 [pubmed]
PHST- 2009/09/18 06:00 [medline]
PHST- 2010/06/15 00:00 [pmc-release]
AID - S0891-5849(09)00178-6 [pii]
AID - 10.1016/j.freeradbiomed.2009.03.018 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2009 Jun 15;46(12):1658-67. doi: 
      10.1016/j.freeradbiomed.2009.03.018. Epub 2009 Mar 31.