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  • Original Paper
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TGF β1 induces prolonged mitochondrial ROS generation through decreased complex IV activity with senescent arrest in Mv1Lu cells

Oncogene volume 24, pages 1895–1903 (2005)Cite this article

Abstract

Transforming growth factor β1 (TGF β1) is a well-characterized cytokine that suppresses epithelial cell growth. We report here that TGF β1 arrested lung epithelial Mv1Lu cells at G1 phase of the cell cycle with acquisition of senescent phenotypes in the presence of 10% serum, whereas it gradually induced apoptosis with lower concentrations of serum. The senescent arrest was accompanied by prolonged generation of reactive oxygen species (ROS) and persistent disruption of mitochondrial membrane potential (ΔΨm). We demonstrated that the sustained ROS overproduction was derived from mitochondrial respiratory defect via decreased complex IV activity and was involved in the arrest. Moreover, we verified that hepatocyte growth factor released Mv1Lu cells from the arrest by protecting mitochondrial respiration, thereby preventing both the ΔΨm disruption and the ROS generation. Our present results suggest the TGF β1-induced senescent arrest as another plausible mechanism to suppress cellular growth in vivo and provide a new biochemical association between the mitochondrial functional defects and the cytokine-induced senescent arrest, emphasizing the importance of maintenance of mitochondrial function in cellular protection from the arrest.

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Abbreviations

ROS:

reactive oxygen species

ΔΨm:

mitochondrial membrane potential

TGF β1:

transforming growth factor β1

HGF:

hepatocyte growth factor

SA-β-gal:

senescence-associated β-galactosidase

DMEM:

Dulbecco's modified Eagle's medium

FBS:

fetal bovine serum

PBS:

phosphate-buffered saline

DNP:

2,4-dinitrophenol

TMPD:

tetramethyl-p-phenylene diamine

PARP:

poly (ADP-ribose) polymerase

NAC:

N-acetylcysteine

DPI:

diphenyleneiodonium chloride

EMT:

epithelial-to-mesenchymal transdifferentiation

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Acknowledgements

We thank Dr Woon Ki Paik for the critical review of this manuscript. This work was supported by the Korea Research Foundation Grant (KRF-2003-041-C00293).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon, 443-721, South Korea

    Young-Sil Yoon, Jae-Ho Lee & Gyesoon Yoon

  2. Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon, 443-721, South Korea

    Sung-Chul Hwang

  3. Institute for Medical Science, Ajou University School of Medicine, San 5, Wonchon-dong, Youngtong-gu, Suwon, 443-721, South Korea

    Kyeong Sook Choi

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  1. Young-Sil Yoon
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Correspondence to Gyesoon Yoon.

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Yoon, YS., Lee, JH., Hwang, SC. et al. TGF β1 induces prolonged mitochondrial ROS generation through decreased complex IV activity with senescent arrest in Mv1Lu cells. Oncogene 24, 1895–1903 (2005). https://doi.org/10.1038/sj.onc.1208262

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