Arachidonic acid-dependent activation of a p22phox-based NAD(P)H oxidase mediates angiotensin II-induced mesangial cell protein synthesis and fibronectin expression via Akt/PKB

Karen Block, Jill M. Ricono, Duck Yoon Lee, Basant Bhandari, Goutam Ghosh-choudhury, Hanna E. Abboud, Yves Gorin

Research output: Contribution to journalArticle

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Abstract

Angiotensin II (Ang II) induces protein synthesis and hypertrophy through arachidonic acid (AA)- and redox-dependent activation of the serine-threonine kinase Akt/PKB in mesangial cells (MCs). The role of NAD(P)II oxidase component p22phox was explored in this signaling pathway and in Ang II-induced expression of the extracellular matrix protein fibronectin. Ang II causes activation of Akt/PKB and induces fibronectin protein expression, effects abrogated by phospholipase A2 inhibition and mimicked by AA. Ang II and AA also elicited an increase in fibronectin expression that was reduced with a dominant negative mutant of Akt/PKB. Exposure of the cells to hydrogen peroxide stimulates Akt/PKB activity and fibronectin synthesis. The antioxidant N-acetylcysteine abolished Ang II- and AA-induced Akt/PKB activation and fibronectin expression. Western blot analysis revealed high levels of p22 phox in MCs. Antisense (AS) but not sense oligonacleotides for p22phox prevented ROS generation in response to Ang II and AA. AS p22phox inhibited Ang II- or AA-induced Akt/PKB as well as protein synthesis and fibronectin expression. These data provide the first evidence, in MCs, of activation by AA of a p22phox-based NAD(P)H oxidase and subsequent generation of ROS. Moreover, this pathway mediates the effect of Ang II on Akt/PKB-induced protein synthesis and fibronectin expression.

Original languageEnglish (US)
Pages (from-to)1497-1508
Number of pages12
JournalAntioxidants and Redox Signaling
Volume8
Issue number9-10
DOIs
StatePublished - Sep 2006

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Mesangial Cells
NADPH Oxidase
Fibronectins
Arachidonic Acid
Angiotensin II
Chemical activation
Proteins
Extracellular Matrix Proteins
Protein-Serine-Threonine Kinases
Phospholipases A2
Acetylcysteine
NAD
Hypertrophy
Hydrogen Peroxide
Oxidation-Reduction
Oxidoreductases
Antioxidants
Western Blotting

ASJC Scopus subject areas

  • Biochemistry

Cite this

Arachidonic acid-dependent activation of a p22phox-based NAD(P)H oxidase mediates angiotensin II-induced mesangial cell protein synthesis and fibronectin expression via Akt/PKB. / Block, Karen; Ricono, Jill M.; Lee, Duck Yoon; Bhandari, Basant; Ghosh-choudhury, Goutam; Abboud, Hanna E.; Gorin, Yves.

In: Antioxidants and Redox Signaling, Vol. 8, No. 9-10, 09.2006, p. 1497-1508.

Research output: Contribution to journalArticle

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abstract = "Angiotensin II (Ang II) induces protein synthesis and hypertrophy through arachidonic acid (AA)- and redox-dependent activation of the serine-threonine kinase Akt/PKB in mesangial cells (MCs). The role of NAD(P)II oxidase component p22phox was explored in this signaling pathway and in Ang II-induced expression of the extracellular matrix protein fibronectin. Ang II causes activation of Akt/PKB and induces fibronectin protein expression, effects abrogated by phospholipase A2 inhibition and mimicked by AA. Ang II and AA also elicited an increase in fibronectin expression that was reduced with a dominant negative mutant of Akt/PKB. Exposure of the cells to hydrogen peroxide stimulates Akt/PKB activity and fibronectin synthesis. The antioxidant N-acetylcysteine abolished Ang II- and AA-induced Akt/PKB activation and fibronectin expression. Western blot analysis revealed high levels of p22 phox in MCs. Antisense (AS) but not sense oligonacleotides for p22phox prevented ROS generation in response to Ang II and AA. AS p22phox inhibited Ang II- or AA-induced Akt/PKB as well as protein synthesis and fibronectin expression. These data provide the first evidence, in MCs, of activation by AA of a p22phox-based NAD(P)H oxidase and subsequent generation of ROS. Moreover, this pathway mediates the effect of Ang II on Akt/PKB-induced protein synthesis and fibronectin expression.",
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