Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle

Nita N. Deshpande, Dan Sorescu, Puvi Seshiah, Masuko Fukai, Marjorie Akers, Qiqin Yin, Kathy K. Griendling

Research output: Contribution to journalArticle

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Abstract

Reactive oxygen species such as hydrogen peroxide (H2O2) can positively and negatively modulate vascular smooth muscle cell (VSMC) growth. To investigate these paradoxical effects of H2O2, we examined its effect on apoptosis, cell cycle progression, and cell cycle proteins. High concentrations of H2O2 (500 μM to 1 mM) induced apoptosis, whereas moderate concentrations (100 μM) caused cell cycle arrest in G1. H2O2 (100 μM) blocked serum-stimulated cyclin-dependent kinase-2 (CDK2) activity, but not CDK4 activity, suggesting that cell cycle arrest occurred in part by inhibiting CDK2 activity. The serum-induced increase in cyclin A mRNA was also completely suppressed by H2O2, whereas cyclin D1 mRNA was not affected. In addition, H2O2 caused a dramatic increase in expression of the cell cycle inhibitor p21 mRNA (9.67 ± 0.94-fold at 2 h) and protein (8.75 ± 0.08-fold at 8 h), but no change in p27 protein. Finally, H2O2 transiently increased p53 protein levels (3.16 ±1.2-fold at 2 h). Thus, whereas high levels of H2O2 induce apoptosis, moderate concentrations of H2O2 coordinate a set of molecular events leading to arrest of VSMCs at the G1/S checkpoint of the cell cycle. These results provide insight into the mechanisms underlying positive and negative regulation of VSMC growth by H2O2 in vascular disease.

Original languageEnglish (US)
Pages (from-to)845-854
Number of pages10
JournalAntioxidants and Redox Signaling
Volume4
Issue number5
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Cell Cycle Checkpoints
Vascular Smooth Muscle
Cyclin-Dependent Kinase 2
Hydrogen Peroxide
G1 Phase Cell Cycle Checkpoints
Muscle
Cells
Apoptosis
Messenger RNA
Smooth Muscle Myocytes
Cell Cycle
Cell growth
Cyclin A
Cell Cycle Proteins
Proteins
Cyclin D1
Growth
Serum
Vascular Diseases
Reactive Oxygen Species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle. / Deshpande, Nita N.; Sorescu, Dan; Seshiah, Puvi; Fukai, Masuko; Akers, Marjorie; Yin, Qiqin; Griendling, Kathy K.

In: Antioxidants and Redox Signaling, Vol. 4, No. 5, 01.01.2002, p. 845-854.

Research output: Contribution to journalArticle

Deshpande, NN, Sorescu, D, Seshiah, P, Fukai, M, Akers, M, Yin, Q & Griendling, KK 2002, 'Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle', Antioxidants and Redox Signaling, vol. 4, no. 5, pp. 845-854. https://doi.org/10.1089/152308602760599007
Deshpande, Nita N. ; Sorescu, Dan ; Seshiah, Puvi ; Fukai, Masuko ; Akers, Marjorie ; Yin, Qiqin ; Griendling, Kathy K. / Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle. In: Antioxidants and Redox Signaling. 2002 ; Vol. 4, No. 5. pp. 845-854.
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