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 language | English (US) |
|---|---|
| Pages (from-to) | 1497-1508 |
| Number of pages | 12 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 8 |
| Issue number | 9-10 |
| DOIs | |
| State | Published - Sep 2006 |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Block, Karen
AU - Ricono, Jill M.
AU - Lee, Duck Yoon
AU - Bhandari, Basant
AU - Ghosh-choudhury, Goutam
AU - Abboud, Hanna E.
AU - Gorin, Yves
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33750897892&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750897892&partnerID=8YFLogxK
U2 - 10.1089/ars.2006.8.1497
DO - 10.1089/ars.2006.8.1497
M3 - Article
C2 - 16987006
AN - SCOPUS:33750897892
VL - 8
SP - 1497
EP - 1508
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 9-10
ER -