Details

Autor(en) / Beteiligte

• Rodriguez-Perez, Ana I.
• Borrajo, Ana
• Rodriguez-Pallares, Jannette
• Guerra, Maria J.
• Labandeira-Garcia, Jose L.

Titel

Interaction between NADPH-oxidase and Rho-kinase in angiotensin II-induced microglial activation

Ist Teil von

• Glia, 2015-03, Vol.63 (3), p.466-482

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2015

Quelle

Wiley Online Library Journals【Remote access available】

Beschreibungen/Notizen

• Previous studies have shown that the brain renin–angiotensin system may play a major role, via angiotensin type 1 (AT1) receptors, in the regulation of neuroinflammation, oxidative stress and progression of dopaminergic degeneration. Angiotensin‐induced activation of the microglial nicotinamide adenine dinucleotide phosphate (NADPH)‐oxidase complex and microglial Rho‐kinase are particularly important in this respect. However, it is not known whether crosstalk between Rho‐kinase and NADPH‐oxidase leads to microglial activation. In the present study, we found that, in the substantia nigra of rats, NADPH‐oxidase activation was involved in angiotensin‐induced Rho‐kinase activation, which, in turn, was involved in angiotensin‐induced NADPH‐oxidase activation. In N9 microglial cell line and primary microglial cultures, a crosstalk signaling between NADPH‐oxidase and Rho‐kinase occurred in a positive feedback fashion during angiotensin‐induced microglial activation. Angiotensin‐induced NADPH‐oxidase activation and superoxide generation led to NF‐кB translocation and Rho‐kinase activation. Rho‐kinase activation was involved in regulation of NADPH‐oxidase activation via p38 mitogen‐activated protein kinase. Moreover, Rho‐kinase activation, via NF‐кB, upregulated AT1 receptor expression in microglial cells through a feed‐forward mechanism. NADPH‐oxidase and Rho‐kinase pathways are known to be responsible for major components of the microglial response, such as changes involving microglial motility and phagocytosis, generation of superoxide, and release of inflammatory cytokines. The present results show that both pathways are linked by a common mechanism that may constitute a basic means of coordinating the microglial response. GLIA 2015;63:466–482 Main Points During angiotensin‐induced microglial activation, NADPH‐oxidase and Rho‐kinase interact in a positive feedback fashion. Furthermore, Rho‐kinase activation, via NF‐кB, upregulates angiotensin type 1 receptors in a feed‐forward mechanism. Angiotensin‐induced NADPH‐oxidase activation leads to NF‐кB translocation and Rho‐kinase activation, which is involved in regulation of NADPH‐oxidase activation via p38 mitogen‐activated protein kinase. As NADPH‐oxidase and Rho‐kinase are known to be responsible for major components of the microglial activation, this mechanism may constitute a basic means of coordinating the microglial response.