Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis

Tanuma, Naoyuki; Sakuma, Hiroshi; Sasaki, Atsushi; Matsumoto, Yoh

doi:10.1007/s00401-006-0083-7

Cited by 208 publications

(175 citation statements)

References 46 publications

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“…Inhibition of GSK-3β activity can increase cell survival during oxidative stress and, as a result, GSK-3β is considered to be a therapeutic target for some neurodegenerative disorders (Balaraman et al, 2006;Chong et al, 2005e;Nurmi et al, 2006;Qin et al, 2006). GSK-3β also may influence inflammatory cell survival and activation (Tanuma et al, 2006). In regard to metabolic disease, inactivation of GSK-3β by small molecule inhibitors or RNA interference prevents toxicity from high concentrations of glucose and increases rat beta cell replication, suggesting a possible target of GSK-3β for pancreatic beta cell regeneration (Mussmann et al, 2007).…”

Section: Epo and Wnt Gsk-3β Nf-κbmentioning

confidence: 99%

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

Maiese

Chong

et al. 2008

Progress in Neurobiology

102

155

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Given that erythropoietin (EPO) is no longer believed to have exclusive biological activity in the hematopoietic system, EPO is now considered to have applicability in a variety of nervous system disorders that can overlap with vascular disease, metabolic impairments, and immune system function. As a result, EPO may offer efficacy for a broad number of disorders that involve Alzheimer's disease, cardiac insufficiency, stroke, trauma, and diabetic complications. During a number of clinical conditions, EPO is robust and can prevent metabolic compromise, neuronal and vascular degeneration, and inflammatory cell activation. Yet, use of EPO is not without its considerations especially in light of frequent concerns that may compromise clinical care. Recent work has elucidated a number of novel cellular pathways governed by EPO that can open new avenues to avert deleterious effects of this agent and offer previously unrecognized perspectives for therapeutic strategies. Obtaining greater insight into the role of EPO in the nervous system and elucidating its unique cellular pathways may provide greater cellular viability not only in the nervous system but also throughout the body.

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Section: Epo and Wnt Gsk-3β Nf-κbmentioning

confidence: 99%

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

Maiese

Chong

et al. 2008

Progress in Neurobiology

102

155

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“…GSK-3β is considered to be a therapeutic target for some neurodegenerative disorders (Balaraman, et al, 2006, Chong, et al, 2005e, Nurmi, et al, 2006, Qin, et al, 2006 and also may to influence inflammatory cell survival and activation (Tanuma, et al, 2006). During models of diabetes, inactivation of GSK-3β by small molecule inhibitors or RNA interference prevents toxicity from high concentrations of glucose and increases rat beta cell replication, suggesting a possible target of GSK-3β for pancreatic beta cell regeneration (Mussmann, et al, 2007).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Erythropoietin and Oxidative Stress

Maiese

Chong

Hou

et al. 2008

CNR

108

113

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Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor κB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care. KeywordsAlzheimer's disease; Akt; angiogenesis; apoptosis; cancer; cardiac; caspases; diabetes; endothelial; erythropoietin; forkhead; FoxO; GSK-3β; inflammation; mitochondria; NF-κB; renal; STATs; Wnt OXIDATIVE STRESSInitial work in pathways that can lead to oxidative stress by early investigators observed that increased metabolic rates could be detrimental to animals in an elevated oxygen environment. More current studies point to the potential aging mechanisms and accumulated toxic effects for an organism that are tied to oxidative stress (Maiese, et al., 2008a NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript in organisms, or at least the rate of oxygen consumption in organisms, has intrigued several investigators. Pearl proposed that increased exposure to oxygen through an increased metabolic rate could lead to a shortened life span (Pearl, 1928). Subsequent work by multiple investigators has furthered this hypothesis by demonstrating that increased metabolic rates could be detrimental to animals in an elevated oxygen environment . When one moves to more current work, oxygen free radicals and mitochondrial DNA mutations have become associated with oxidative stress injury, aging mechanisms, and accumulated toxicity for an organism (Yui and Matsuura, 2006).Oxygen free radicals can be generated in elevated quantities during the reduction of oxygen and subsequently lead to cell injury and apoptosis. Oxidative stress occurs as a result of the development of reactive oxygen species that consist of oxygen free radicals and other chemical entities. These agents can involve superoxide free radicals, hydrogen peroxide, sin...

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“…I-TAC reportedly signals through CXCR7 and CXCR3 (Burns et al, 2006). Moreover, CXCR3 was previously shown to be expressed by astrocytes in vitro and in vivo (Biber et al, 2002;Goldberg et al, 2001;Subileau et al, 2009;Tanuma et al, 2006). This prompted us to additionally examine I-TAC-dependent signaling in astrocytes with RNAi-mediated inhibition of CXCR3 expression.…”

mentioning

confidence: 99%

The presumed atypical chemokine receptor CXCR7 signals through G_i/o proteins in primary rodent astrocytes and human glioma cells

Ödemis¹,

Lipfert²,

Kraft³

et al. 2011

Glia

112

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SDF-1/CXCL12 binds to the chemokine receptors, CXCR4 and CXCR7, and controls cell proliferation and migration during development, tumorigenesis, and inflammatory processes. It is currently assumed that CXCR7 would represent an atypical or scavenger chemokine receptor which modulates the function of CXCR4. Contrasting this view, we demonstrated recently that CXCR7 actively mediates SDF-1 signaling in primary astrocytes. Here, we provide evidence that CXCR7 affects astrocytic cell signaling and function through pertussis toxin-sensitive G i/o proteins. SDF-1-dependent activation of G i/o proteins and subsequent increases in intracellular Ca 21 concentration persisted in primary rodent astrocytes with depleted expression of CXCR4, but were abolished in astrocytes with depleted expression of CXCR7. Moreover, CXCR7-mediated effects of SDF-1 on Erk and Akt signaling as well as on astrocytic proliferation and migration were all sensitive to pertussis toxin. Likewise, pertussis toxin abolished SDF-1-induced activation of Erk and Akt in CXCR7-only expressing human glioma cell lines. Finally, consistent with a ligand-biased function of CXCR7 in astrocytes, the alternate CXCR7 ligand, I-TAC/CXCL11, activated Erk and Akt through b-arrestin. The demonstration that SDF-1-bound CXCR7 activates G i/o proteins in astrocytes could help to explain some discrepancies previously observed for the function of CXCR4 and CXCR7 in other cell types. V

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Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis

Cited by 208 publications

References 46 publications

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

Erythropoietin and Oxidative Stress

The presumed atypical chemokine receptor CXCR7 signals through G_i/o proteins in primary rodent astrocytes and human glioma cells

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Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis

Cited by 208 publications

References 46 publications

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

Erythropoietin: Elucidating new cellular targets that broaden therapeutic strategies

Erythropoietin and Oxidative Stress

The presumed atypical chemokine receptor CXCR7 signals through Gi/o proteins in primary rodent astrocytes and human glioma cells

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Product

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The presumed atypical chemokine receptor CXCR7 signals through G_i/o proteins in primary rodent astrocytes and human glioma cells