Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

Min, Kyoung‐jin; Yang, Myung-Soon; Jou, Ilo; Joe, Eun‐Hye

doi:10.1038/emm.2004.58

Cited by 27 publications

(19 citation statements)

References 41 publications

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“…Interestingly, inhibition of PKA with H89, together with α-MSH, gave rise to a decrease in cell viability. PKA, a downstream mediator of MCR signalling, has been shown to activate murine microglial cells not previously activated (Min et al, 2004). However, inhibition of PKA did not reduce the α-MSH-induced release of IL-6 from the human microglia.…”

Section: Discussionmentioning

confidence: 70%

Cytokine production by a human microglial cell line: Effects of ßamyloid and α-melanocyte-stimulating hormone

et al. 2005

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Senile plaques in the Alzheimer's disease (AD) are formed by aggregation of beta-amyloid (Abeta) peptide. Abeta peptide has been shown to activate microglia and stimulate their production of inflammatory factors, such as cytokines. In the AD brain, the continued presence of amyloid plaques may keep microglia persistently activated, leading to chronic inflammation in the CNS. It is well established that alpha-melanocyte-stimulating hormone (alpha-MSH) gives rise to anti-inflammatory and anti-pyretic effects. The biological activities of alpha-MSH are mediated by one or more of the melanocortin receptor (MCR) subtypes, i.e. MCR1 - MCR5. The aim of the present study was to determine the effect of alpha-MSH alone and on Abeta-activated microglial cells with regard to the secretion of inflammatory cytokines, such as interleukin-6 (IL-6), and to determine which receptor subtype mediates the effects of alpha-MSH. The human microglial cell line, CHME3, was incubated for 24 h with freshly dissolved Abeta(1-40), interferon-gamma (IFN-gamma) and/or alpha-MSH. Freshly dissolved Abeta(1-40) (5-60 microM) resulted in a dose-dependent decrease in cell viability, along with a dose-dependent increase in IL-6 release. Neither IFN-gamma nor alpha-MSH affected the Abeta-induced secretion of IL-6, but resulted in a dose-dependent increase in basal IL-6 release. Agouti, the endogenous antagonist of MCR1 and 4, further increased the alpha-MSH-induced secretion of IL-6. RT-PCR showed the expression of MCR1, MCR3, MCR4 and MCR5 mRNA. The combined data suggest that the effect of alpha-MSH in increasing IL-6 release from the human microglial cell line is mediated by MCR3 or MCR5.

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Section: Discussionmentioning

confidence: 70%

Cytokine production by a human microglial cell line: Effects of ßamyloid and α-melanocyte-stimulating hormone

et al. 2005

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“…To examine whether PKA is stimulated by shear stress, I first explored the phosphorylation of CREB, one of the well known regulatory targets of PKA (Daniel et al, 1998;Park et al, 2003;Min et al, 2004). When the BAECs were exposed to shear stress, there was a significant increase in CREB phosphorylation at Ser133, maximizing at 30 min from the onset of shear stress ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Shear stress stimulates phosphorylation of protein kinase A substrate proteins including endothelial nitric oxide synthase in endothelial cells

Boo

2006

Exp Mol Med

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Fluid shear stress plays a critical role in vascular health and disease. While protein kinase A (PKA) has been implicated in shear-stimulated signaling events in endothelial cells, it remains unclear whether and how PKA is stimulated in response to shear stress. This issue was addressed in the present study by monitoring the phosphorylation of endogenous substrates of PKA. Shear stress stimulated the phosphorylation of cAMP responsive element binding protein (CREB) in a PKA-dependent manner. Western blot analysis using the antibody reactive against the consensus motif of PKA substrates detected two proteins, P135 and P50, whose phosphorylation was increased by shear stress. The phosphorylation of P135 was blocked by a PKA inhibitor, H89, but not by a phosphoinositide 3-kinase inhibitor, wortmannin. Expression of a constitutively active PKA subunit stimulated P135 phosphorylation, supporting the potential of P135 as a PKA substrate. P135 was identified as endothelial nitric oxide synthase (eNOS) by immunoprecipitation study. PKA appeared to mediate shear stress-stimulated eNOS activation. Shear stress stimulated intracellular translocation of PKA activity from 'soluble' to 'particulate' fractions without involving cellular cAMP increase. Taken together, this study suggests that shear stress stimulates PKA-dependent phosphorylation of target proteins including eNOS, probably by enhancing intracellular site-specific interactions between protein kinase and substrates.

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“…3A-C). Likewise, although some evidence exists that suggests the cAMP-dependent protein kinase (PKA) may participate in activation of NF-B (Baeuerle and Henkel, 1994;Min et al, 2004), the PKA inhibitor KT5720 (1 M) had no effect on DHPG-induced activation of p50, p65, or c-Rel in area CA1 of the hippocampus (Fig. 3A-C).…”

Section: Signaling Pathways Coupling Gpi-mglurs With Nf-bmentioning

confidence: 97%

Regulation of Nuclear Factor κB in the Hippocampus by Group I Metabotropic Glutamate Receptors

O’Riordan¹,

Huang²,

Pizzi³

et al. 2006

J. Neurosci.

102

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Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

Abstract: Abbreviations: CRE, cAMP response element; IL-1β, interleukin-1β; iNOS, inducible nitric oxide synthase; NF-κB, nuclear factor-kappa B; PKA, protein kinase A; TNF-α, tumor necrosis factor-α

Cited by 27 publications

References 41 publications

Cytokine production by a human microglial cell line: Effects of ßamyloid and α-melanocyte-stimulating hormone

Cytokine production by a human microglial cell line: Effects of ßamyloid and α-melanocyte-stimulating hormone

Shear stress stimulates phosphorylation of protein kinase A substrate proteins including endothelial nitric oxide synthase in endothelial cells

Regulation of Nuclear Factor κB in the Hippocampus by Group I Metabotropic Glutamate Receptors

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