Microglia-derived IGF-2 prevents TNFα induced death of mature oligodendrocytes in vitro

Nicholas, Richard; Stevens, Sarah; Wing, Mark; Compston, D. A. S.

doi:10.1016/s0165-5728(02)00011-5

Cited by 78 publications

(55 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microglia can also secrete trophic factors, which could support damaged cells and induce repair. In vitro studies have demonstrated that microglia can either be directly toxic to oligodendrocytes (Nicholas et al, 2003;Li et al, 2005) or can support oligodendrocyte survival (Pang et al, 2000;Nicholas et al, 2001Nicholas et al, , 2002, with the predominant effect being context dependant. Dichotomous effects of microglia also appear to occur in vivo with reports of either deleterious Mana et al, 2006;Pasquini et al, 2007) or protective effects in response to cuprizone-induced demyelination, the latter particularly predominant during the remyelination phase (Arnett et al, 2001(Arnett et al, , 2002(Arnett et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination

Binder¹,

Cate²,

Prieto³

et al. 2008

J. Neurosci.

116

110

View full text Add to dashboard Cite

The TAM family of receptor protein tyrosine kinases comprises three known members, namely Tyro3, Axl, and Mer. These receptors are widely expressed in the nervous system, including by oligodendrocytes, the cell type responsible for myelinating the CNS. We examined the potential role of the TAM family and of their principle cognate ligand, Gas6 (growth arrest gene 6), in modulating the phenotype of the cuprizone model of demyelination. We found that the expression profiles of Axl, Mer, and Gas6 mRNA were increased in the corpus callosum in a temporal profile correlating with the increased migration and proliferation of microglia/macrophages in this model. In contrast, expression of Tyro3 decreased, correlating with the loss of oligodendrocytes. Gas6 both promoted in vitro survival of oligodendrocytes (39.3 Ϯ 3.1 vs 11.8 Ϯ 2.4%) and modulated markers of activation in purified cultures of microglia (tumor necrosis factor ␣ mRNA expression was reduced ϳ48%). In Gas6 Ϫ/Ϫ mice subjected to cuprizone-challenge, demyelination was greater than in control mice, within the rostral region of the corpus callosum, as assessed by luxol fast blue staining (myelination reduced by 36%) and by ultrastructural analysis. An increased loss of Gst-(glutathione S-transferase-)-positive oligodendrocytes was also identified throughout the corpus callosum of Gas6 Ϫ/Ϫ mice. Microglial marker expression (ionized calcium-binding adapter molecule 1) was increased in Gas6 Ϫ/Ϫ mice but was restricted to the rostral corpus callosum. Therefore, TAM receptor activation and regulation can independently influence both oligodendrocyte survival and the microglial response after CNS damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination

Binder¹,

Cate²,

Prieto³

et al. 2008

J. Neurosci.

116

110

View full text Add to dashboard Cite

show abstract

“…It has been shown that OPCs are more sensitive to environmental stress signals than more mature OLs. 16,17 For example, we have previously reported that treatment of OPCs with selected stress signals, such as ultraviolet radiation, dramatically decreases their survival in a time-and dose-dependent manner, while postmitotic OLs are resistant. 18 This selective vulnerability is, in part, due to the downregulation of Jun N-terminal kinase (JNK) 3 expression and activity during OL differentiation.…”

Section: Defined Stages Of Ol Developmentmentioning

confidence: 99%

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

2008

View full text Add to dashboard Cite

Apoptosis plays a crucial role in brain development by ensuring that only appropriately growing, migrating, and synapse-forming neurons and their associated glial cells survive. This process involves an intimate relationship between cell-cell interactions and developmental cues and is further impacted by environmental stress during neurogenesis and disease. Oligodendrocytes (OLs), the major myelin-forming cells in the central nervous system, largely form after this wave of neurogenesis but also show a selective vulnerability to cell death stimuli depending on their stage of development. This can affect not only embryonic and early postnatal brain formation but also the response to demyelinating pathologies. In the present review, we discuss the stagespecific sensitivity of OL lineage cells to damage-induced death and how this might impact myelin survival and regeneration during injury or disease. Apoptosis is a major form of programmed cell death required for the normal development of metazoan tissues, including the brain. 1 During embryonic development of the brain, many more cells than ultimately needed are generated and then selection occurs, resulting in the apoptotic depletion of the surplus cells. The importance of the apoptotic pathway in early brain development has been demonstrated by the targeted deletion in mice of the death-specific cysteine proteases caspase-3 or caspase-9, or of the co-activator Apaf-1, all of which cause severe brain overgrowth and perinatal death. 2,3 In the adult brain, 90% of the cells belong to the glial lineage, which includes oligodendrocytes (OLs), astrocytes and microglia. The glia ensures proper development, function and repair of the neuronal network. This is possible through continuous cross-talk between the glia and neurons mediated by neurotransmitters, cytokines, growth and trophic factor secretion and signaling in a reciprocal manner. [4][5][6][7] In the central nervous system (CNS), OLs are responsible for axon myelination, which insulates the electrical signals transmitted between neurons. OL and neuron development is tightly regulated and the myelin sheath is constructed only when OLs reach maturity and neurons have grown appropriately. In response to injury or during the course of neurological diseases, the neuron-glia network can be replenished to some extent but the degree of repair is dependent on the developmental stage of the OL. This complexity is compounded by the differential sensitivity of OL lineage cells to apoptotic stimuli. In the present review, we will first briefly examine the stages of differentiation of OL cells and then discuss several diseases that are impacted by OL apoptosis, noting how the stage of cell differentiation governs the sensitivity to apoptosis. Defined Stages of OL DevelopmentOligodendrocyte development can be divided into four distinct stages according to the temporal expression of cell surface markers and morphology (Table 1). 8 In the first stage, OL progenitor cells (OPCs) originate from the neuroepithelium of the ventricul...

show abstract

“…IGF-1 and IGF-2 inhibits TNF-␣-induced JNK activation in HEK 293 (10) and CG4 cell lines, respectively (20). Recently, we have shown that TNF-␣ also induces MLK3 activity in Jurkat T Cells (22) and that TNF-␣-induced cell death was inhibited by CEP-11004, a specific mixed lineage kinase inhibitor in PC-12 cells (21).…”

Section: Fig 2 Endogenous and Recombinant Mlk3 Interact With Akt Anmentioning

confidence: 99%

Negative Regulation of Mixed Lineage Kinase 3 by Protein Kinase B/AKT Leads to Cell Survival

Barthwal¹,

Sathyanarayana²,

Kundu³

et al. 2003

Journal of Biological Chemistry

131

125

View full text Add to dashboard Cite

Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAPKKK) that activates c-jun N-terminal kinase (JNK) and can induce cell death in neurons. By contrast, the activation of phosphatidylinositol 3-kinase and AKT/protein kinase B (PKB) acts to suppress neuronal apoptosis. Here, we report a functional interaction between MLK3 and AKT1/PKB␣. Endogenous MLK3 and AKT1 interact in HepG2 cells, and this interaction is regulated by insulin. The interaction domain maps to the C-terminal half of MLK3 (amino acids 511-847), and this region also contains a putative AKT phosphorylation consensus sequence. Endogenous JNK, MKK7, and MLK3 kinase activities in HepG2 cells are significantly attenuated by insulin treatment, whereas the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin reversed the effect. Finally, MLK3-mediated JNK activation is inhibited by AKT1. AKT phosphorylates MLK3 on serine 674 both in vitro and in vivo. Furthermore, the expression of activated AKT1 inhibits MLK3-mediated cell death in a manner dependent on serine 674 phosphorylation. Thus, these data provide the first direct link between MLK3-mediated cell death and its regulation by a cell survival signaling protein, AKT1.The cellular decision to undergo either cell death or cell survival is determined by the integration of multiple survival and death signals. Mixed lineage kinase 3 (MLK3) 1 is a member of a growing family of mixed lineage kinases (1). Recently, it has been shown that overexpression of MLK3 or NGF withdrawal leads to neuronal cell death, which can be prevented by treatment with a small molecule inhibitor of MLKs, CEP-1347 (2). Similarly, CEP-11004, an analog of CEP-1347, has also been shown to prevent neuronal cell death upon NGF withdrawal (3). These results indicate a significant and direct involvement of MLKs in regulating cell death; however, the detailed mechanism by which MLKs are regulated is still unknown.The c-jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is stimulated by proinflammatory cytokines, oxidative stress, heat shock, UV, ␥-irradiation, and by other cellular stresses (4, 5). The signals in stress-activated JNK pathway are transmitted through three core modules: MAP3Ks such as members of the mixed lineage kinases or MEKK members, a MAP2K such as SEK1/MKK4 or MKK7, and MAPK such as JNK family members (4, 5). The activated MAP3K phosphorylates and activates MKK7 or SEK1, which in turn phosphorylates and activates JNK. JNKs phosphorylate several nuclear transcription factors that include ELK1, c-Jun, and ATF2 (4, 5). In several cell types, the activation of JNKs is directly linked to cell death (6 -8). Therefore, one mechanism of cell survival could be to block JNK pathway induction. The activation of phosphatidylinositol 3-kinase (PI3K) correlates with increased cell survival, and this effect is largely mediated through the activation of a serine/threonine kinase, AKT (also known as PKB). PI3K agonists such as insulin and insulin-like growth factor-1 (IGF-1) ...

show abstract

Microglia-derived IGF-2 prevents TNFα induced death of mature oligodendrocytes in vitro

Cited by 78 publications

References 24 publications

Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination

Gas6 Deficiency Increases Oligodendrocyte Loss and Microglial Activation in Response to Cuprizone-Induced Demyelination

Maturation-dependent sensitivity of oligodendrocyte lineage cells to apoptosis: implications for normal development and disease

Negative Regulation of Mixed Lineage Kinase 3 by Protein Kinase B/AKT Leads to Cell Survival

Contact Info

Product

Resources

About