Calcium-dependent Tetramer Formation of S100A8 and S100A9 is Essential for Biological Activity

Leukert, Nadja; Vogl, Thomas; Strupat, Kerstin; Reichelt, Rudolf; Sorg, Clemens; Roth, Johannes

doi:10.1016/j.jmb.2006.04.009

Cited by 168 publications

(169 citation statements)

References 42 publications

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“…S100A8 and S100A9 play many important roles including regulation of enzyme activity, Ca 2+ -homeostasis, and interaction with components of the cytoskeleton. [14-16] But experimental data indicate a positive feedback mechanism according to which S100A8 and S100A9, released by primed myeloid cells under inflammatory conditions, promotes further leukocyte recruitment. The heterodimeric complex is involved in innate immunity, leukocyte adhesion, and endothelial transmigration.…”

Section: Discussionmentioning

confidence: 99%

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Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

Sun

Zhang

et al. 2013

World Journal of Emergency Medicine

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BACKGROUND:Recent studies have showed that S100A8 has been implicated in the pathobiology of inflammatory disorders, and that cerebral ischemia reperfusion (I/R) rapidly activates inflammation responses via Toll-like receptor 4 (TLR4). This study aimed to explore the expression of S100A8 and the relationship between S100A8 and TLR4 in focal cerebral ischemia reperfusion injury.METHODS:C3H/HeJ mice (n=30) and C3H/HeN mice (n=30) were divided randomly into a C3H/HeJ model group (n=18), a C3H/HeJ control group (n=12), a C3H/HeN model group (n=18), and a C3H/HeN control group (n=12). Middle cerebral artery I/R model in mice was produced using a thread embolism method. The brains of the mice were collected after ischemia for 1 hour and reperfusion for 12 hours. Stroke outcome was evaluated by determination of infarct volume and assessment of neurological impairment scores. Brain injury after cerebral I/R was observed by an optical microscope after TTC and HE dyeing. The immunofluorescence technique and real time PCR were used to test the expression level of S100A8 in brain damage.RESULTS:Compared with C3H/HeN mice, TLR4-deficient mice (C3H/HeJ) had lower infarct volumes and better outcomes in neurological tests. The levels of S100A8 increased sharply in the brains of mice after I/R injury. In addition, mice that lacked TLR4 (C3H/HeJ) had lower expression of I/R-induced S100A8 than C3H/HeN mice in the model group, indicating that a close relationship might exist between the levels of S100A8 and TLR4.CONCLUSION:S100A8 interaction with TLR4 might be involved in brain damage and in inflammation triggered by I/R injury.

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Section: Discussionmentioning

confidence: 99%

“…Recent clinical studies[16] have been focused on elevated serum levels of S100A8 with inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and chronic lung disease. Moreover, increased S100A8/A9 expression has become a novel, early, and sensitive marker of acute coronary syndromes.…”

Section: Discussionmentioning

confidence: 99%

Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

Sun

Zhang

et al. 2013

World Journal of Emergency Medicine

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“…Then failure of tetramer formation was associated with a lack of functional activity of S100A8/S100A9 complexes in promoting the formation of microtubules (37).…”

Section: Discussionmentioning

confidence: 99%

The establishment of two paclitaxel‐resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines

et al. 2007

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“…Calcium binding induces tetramer formation or oligomerization of S100A8 and S100A9, a prerequisite for their biological activities (16). The conformational changes allow the phosphorylation of S100A9 by p38 MAPK and polymerization of microtubules during migration of phagocytes (12).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies showed that S100 proteins form tetramers or even higher-order oligomers in a calcium-dependent manner, and that oligomerization is an essential prerequisite for their biological functions (16,17). To further investigate the significance of S100A8/S100A9 in H-Ras -mediated cell invasion/migration, we temporarily depleted intracellular calcium in H-Ras MCF10A cells using BAPTA/AM, an intracellular calcium chelator (18).…”

Section: Role Of Calcium In Invasion Migration and S100a8/a9 Expresmentioning

confidence: 99%

Global Gene Expression Profiling Unveils S100A8/A9 as Candidate Markers in H-Ras-Mediated Human Breast Epithelial Cell Invasion

Moon

Hao

Song

et al. 2008

Molecular Cancer Research

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The goal of the present study is to unveil the gene expression profile specific to the biological processes of human breast epithelial cell invasion and migration using an MCF10A model genetically engineered to constitutively activate the H-ras or N-ras signaling pathway. We previously showed that H-Ras, but not N-Ras, induces MCF10A cell invasion/migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. Thus, these cell lines provide an experimental system to separate the gene expression profile associated with cell invasion apart from cell proliferation/transformation. Analysis of whole human genome microarray revealed that 412 genes were differentially expressed among MCF10A, N-Ras MCF10A, and H-Ras MCF10A cells and hierarchical clustering separated 412 genes into four clusters. We then tested whether S100A8 and S100A9, two of the genes which are most highly up-regulated in an H-Ras -specific manner, play a causative role for H-Ras -mediated MCF10A cell invasion and migration. Importantly, small interfering RNA -mediated knockdown of S100A8/A9 expression significantly reduced H-Ras -induced invasion/ migration. Conversely, the induction of S100A8/A9 expression conferred the invasive/migratory phenotype to parental MCF10A cells. Furthermore, we provided evidence of signaling cross-talk between S100A8/A9 and the mitogen-activated protein kinase signaling pathways essential for H-Ras -mediated cell invasion and migration. Taken together, this study revealed S100A8/A9 genes as candidate markers for metastatic potential of breast epithelial cells. Our gene profile data provide useful information which may lead to the identification of additional potential targets for the prognosis and/or therapy of metastatic breast cancer. (Mol Cancer Res 2008;6(10):1544 -53)

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Calcium-dependent Tetramer Formation of S100A8 and S100A9 is Essential for Biological Activity

Cited by 168 publications

References 42 publications

Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

Upregulated expression of S100A8 in mice brain after focal cerebral ischemia reperfusion

The establishment of two paclitaxel‐resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines

Global Gene Expression Profiling Unveils S100A8/A9 as Candidate Markers in H-Ras-Mediated Human Breast Epithelial Cell Invasion

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