Gene interactions and pathways from curated databases and text-mining
Br J Pharmacol 2008, PMID: 17906677

Enhanced angiotensin converting enzyme 2 regulates the insulin/Akt signalling pathway by blockade of macrophage migration inhibitory factor expression.

Zhong, J-C; Yu, X-Y; Lin, Q-X; Li, X-H; Huang, X-Z; Xiao, D-Z; Lin, S-G

OBJECTIVE

Macrophage migration inhibitory factor (MIF) is now known to be a pro-inflammatory cytokine associated with insulin resistance. Our aim was to investigate whether angiotensin converting enzyme 2 (ACE2) could modulate the expression of MIF and the insulin/Akt-endothelial nitric oxide (NO) synthase (eNOS) signalling in a human endothelial cell line (EAhy926).

METHODS

A recombinant plasmid encompassing human ACE2 gene was constructed and transfected into the EAhy926 cells. The mRNA, phosphorylation and protein levels of p22phox, MIF, Akt and eNOS in endothelial cells were determined by real-time PCR and Western blot analysis, respectively.

RESULTS

Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells. In addition, Ang II diminished insulin-stimulated phosphorylation of Akt (at Ser(473)) and eNOS (at Ser(1177)) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells.

CONCLUSIONS

The results reveal that gene transfer of ACE2 regulated Ang II-mediated impairment of insulin signalling and involved the Akt-eNOS phosphorylation pathway. These beneficial effects of ACE2 overexpression appear to result mainly from blocking MIF expression in endothelial cells, suggesting that the ACE2 gene may be a novel therapeutic target for diseases related to inflammation and insulin resistance.

Diseases/Pathways annotated by Medline MESH: Insulin Resistance
Document information provided by NCBI PubMed

Text Mining Data

p22phox ⊣ ACE2: " Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells "

MIF ⊣ ACE2: " Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells "

p22phox → angiotensin (Ang) II: " Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells "

MIF → angiotensin (Ang) II: " Gene transfer of ACE2 suppressed the expression of p22phox and MIF induced by angiotensin (Ang) II and Ang IV, accompanied by a decreased level of malondialdehyde in cells "

Akt ⊣ Ang II: " In addition, Ang II diminished insulin stimulated phosphorylation of Akt ( at Ser ( 473 ) ) and eNOS ( at Ser ( 1177 ) ) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells "

eNOS ⊣ Ang II: " In addition, Ang II diminished insulin stimulated phosphorylation of Akt ( at Ser ( 473 ) ) and eNOS ( at Ser ( 1177 ) ) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells "

Akt → insulin: " In addition, Ang II diminished insulin stimulated phosphorylation of Akt ( at Ser ( 473 ) ) and eNOS ( at Ser ( 1177 ) ) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells "

eNOS → insulin: " In addition, Ang II diminished insulin stimulated phosphorylation of Akt ( at Ser ( 473 ) ) and eNOS ( at Ser ( 1177 ) ) and NO generation, effects which were reversed by ACE2 gene transfer and anti-MIF treatment in endothelial cells "

Manually curated Databases

No curated data.