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Original

Mitochondrial reactive oxygen species originating from Romo1 exert an important role in normal cell cycle progression by regulating p27Kip1 expression

, , , , , , & show all
Pages 729-737 | Received 03 Dec 2008, Published online: 19 Jan 2010
 

Abstract

Reactive oxygen species (ROS) steady-state levels are required for entry into the S phase of the cell cycle in normal cells, as well as in tumour cells. However, the contribution of mitochondrial ROS to normal cell proliferation has not been well investigated thus far. A previous report showed that Romo1 was responsible for the high ROS levels in tumour cells. Here, we show that endogenous ROS generated by Romo1 are indispensable for cell cycle transition from G1 to S phase in normal WI-38 human lung fibroblasts. The ROS level in these cells was down-regulated by Romo1 knockdown, resulting in cell cycle arrest in the G1 phase. This arrest was associated with an increase in the level of p27Kip1. These results demonstrate that mitochondrial ROS generated by Romo1 expression is required for normal cell proliferation and it is suggested that Romo1 plays an important role in redox signalling during normal cell proliferation.

Abbreviations
ROS=

reactive oxygen species

Romo1=

reactive oxygen species modulator 1

siRNA=

small interfering RNA

PDL=

population doublings

NAC=

N-acetyl cysteine

H2O2=

hydrogen peroxide

PBS=

phosphate-buffered saline

MAPK=

Mitogen-activated protein kinase

Erk=

extracellular-signal-regulated kinase

MnSOD=

manganese superoxide dismutase

FITC=

fluorescein isothiocyanate

FBS=

foetal bovine serum

RT-PCR=

reverse transcription-polymerase chain reaction

BrdU=

5-bromo-2-deoxyuridine

MOI=

multiplicity of infection

Abbreviations
ROS=

reactive oxygen species

Romo1=

reactive oxygen species modulator 1

siRNA=

small interfering RNA

PDL=

population doublings

NAC=

N-acetyl cysteine

H2O2=

hydrogen peroxide

PBS=

phosphate-buffered saline

MAPK=

Mitogen-activated protein kinase

Erk=

extracellular-signal-regulated kinase

MnSOD=

manganese superoxide dismutase

FITC=

fluorescein isothiocyanate

FBS=

foetal bovine serum

RT-PCR=

reverse transcription-polymerase chain reaction

BrdU=

5-bromo-2-deoxyuridine

MOI=

multiplicity of infection

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