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Modulation of angiotensin II signaling for GATA4 activation by homocysteine

Y J Suzuki1, S S Shi, J B Blumberg

  • 1Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111, USA. SUZUKI_LP@HNRC.TUFTS.EDU

Antioxidants & Redox Signaling
|March 7, 2001
PubMed

Insights

Homocysteine (Hcy) alters angiotensin II (Ang II) signaling, delaying GATA4 and NFAT activation in cells. This suggests Hcy contributes to cardiovascular disease by modulating Ang II pathways.

Area of Science:

  • Cardiovascular biology
  • Molecular signaling
  • Cellular mechanisms

Background:

  • Homocysteine (Hcy) is a pro-oxidant compound implicated in cardiovascular pathology.
  • Angiotensin II (Ang II) plays a key role in age-associated cardiovascular diseases.
  • GATA4 transcription factor is a recognized mediator of heart failure.

Purpose of the Study:

  • To investigate the interrelationship between Homocysteine, Angiotensin II, and GATA4 activity.
  • To determine how Homocysteine affects Angiotensin II signaling pathways.
  • To elucidate the role of these elements in cellular gene transcription.

Main Methods:

  • Utilized NIH/3T3 fibroblasts for experimental analysis.
  • Employed Electrophoretic Mobility Shift Assays (EMSA) to assess DNA binding activity.
  • Performed supershift analysis to identify specific transcription factors.

Main Results:

  • Angiotensin II (Ang II) induced transient DNA binding activity to the GATA consensus sequence, identified as GATA4.
  • Ang II also induced Nuclear Factor of Activated T-cells (NFAT) activity with similar kinetics.
  • Pretreatment with Homocysteine (Hcy) delayed the peak activation of Ang II-induced NFAT and GATA by 30 minutes.
  • Hcy also delayed Ang II-mediated activation of c-fos serum response factor (SRF).

Conclusions:

  • Homocysteine (Hcy) modulates Angiotensin II (Ang II) signaling pathways.
  • Hcy's pathogenic effects in the cardiovascular system may involve altering Ang II-mediated gene transcription.
  • These findings highlight a novel mechanism linking Hcy, Ang II, and GATA4 in cardiovascular disease progression.

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