Neuroprotection by transforming growth factor-β1 involves activation of nuclear factor-κB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1,2 signaling pathways

Zhu, Yuan; Culmsee, Carsten; Klumpp, Susanne; Krieglstein, Josef

doi:10.1016/j.neuroscience.2003.10.037

Cited by 146 publications

(88 citation statements)

References 50 publications

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“…The best studied exception to this observation occurs in tumor cells in which various alterations in the TGF-β signaling pathway allows for escape from the pro-apoptotic effects of TGF-β. TGF-β has been shown to promote neuronal cell survival by stimulation and activation of ALK1, an alternate TGF-β receptor, resulting in activation and phosphorylation of SMADs 1 and 5 (data not shown) [50][51][52]. In studies of Konig et al [18], TGF-β stimulated neuronal cell ALK1, but not ALK5/ TβRI, expression within one hour of TGF-β treatment.…”

Section: Discussionmentioning

confidence: 83%

TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival

Gingery

Bradley

Pederson

et al. 2008

Experimental Cell Research

162

120

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To better understand the roles of TGF-β in bone metabolism, we investigated osteoclast survival in response TGF-β and found that TGF-β inhibited apoptosis. We examined the receptors involved in promotion of osteoclast survival and found that the canonical TGF-β receptor complex is involved in the survival response. The upstream MEK kinase TAK1 was rapidly activated following TGF-β treatment. Since osteoclast survival involves MEK, AKT, and NFκB activation, we examined TGF-β effects on activation of these pathways and observed rapid phosphorylation of MEK, AKT, IKK, IκB, and NFκB. The timing of activation coincided with SMAD activation and dominant negative SMAD expression did not inhibit NFκB activation, indicating that kinase pathway activation is independent of SMAD signaling. Inhibition of TAK1, MEK, AKT, NIK, IKK, or NFκB repressed TGF-β-mediated osteoclast survival. Adenoviral-mediated TAK1 or MEK inhibition eliminated TGF-β-mediated kinase pathway activation and constitutively active AKT expression overcame apoptosis induction following MEK inhibition. TAK1/MEK activation induces pro-survival BclX L expression and TAK1/MEK and SMAD pathway activation induces pro-survival Mcl-1 expression. These data show that TGF-β-induced NFκB activation is through TAK1/MEK-mediated AKT activation, which is essential for TGF-β to support of osteoclast survival.

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Section: Discussionmentioning

confidence: 83%

TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival

Gingery

Bradley

Pederson

et al. 2008

Experimental Cell Research

162

120

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“…Concentration of E 2 (10 nM), wortmannin [30 nM; IC 50 of 5 nM for PI3K (Arcaro and Wymann, 1993)], PD 98059 [20 M; IC 50 of 5 M for MAPK (Borsch-Haubold et al, 1996)], UO126 [20 M; IC 50 of 72 and 58 nM for MAP kinase kinase 1 (MEK1) and MEK2 (Duncia et al, 1998)], and UO124 (20 M) were based on literature (Qiu et al, 1998;Simoncini et al, 2000Simoncini et al, , 2004Simoncini et al, , 2005Zhu et al, 2004;Wu et al, 2005). The concentration of wortmannin (30 nM) and LY294004 [2-(4-morpholinyl)-8-phenyl-1(4 H)-benzopyran-4-one] (20 M) used in the present study were selected to maximally inhibit PI3K Ͼ99% and to minimize nonspecific inhibition of MAPK Ͻ4% (Davies et al, 2000).…”

Section: Methodsmentioning

confidence: 99%

“…*p Ͻ 0.05 versus control neurons; **p Ͻ 0.01 versus control neurons. Con, Control. between the PI3K and MAPK signaling pathways (Qiu et al, 1998;Zhu et al, 2004).…”

Section: E 2 Increased Akt and Erk1/2 Phosphorylation In A Time-depenmentioning

confidence: 99%

Estrogen Receptor Protein Interaction with Phosphatidylinositol 3-Kinase Leads to Activation of Phosphorylated Akt and Extracellular Signal-Regulated Kinase 1/2 in the Same Population of Cortical Neurons: A Unified Mechanism of Estrogen Action

Mannella¹,

Brinton²

2006

J. Neurosci.

190

189

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17␤-Estradiol (E 2 )-induced neuroprotection is dependent on mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) signaling cascades. We sought to determine whether E 2 neuroprotective mechanisms are mediated by a unified signaling cascade activated by estrogen receptor (ER)-PI3K interaction within the same population of neurons or whether E 2 activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt are independent signaling events in different neuronal populations. Immunoprecipitation of E 2 -treated cortical neurons was conducted to determine a protein-protein interaction between ER and the PI3K regulatory subunit p85. Subsequently, cortical neurons were treated with E 2 alone or in presence of MAPK inhibitors or PI3K inhibitors. Results of these analyses indicated a protein-protein interaction between ER and p85 that was time-dependent and consistent with the temporal profile for generation of Akt (pAkt) and ERK1/2 phosphorylation (pERK1/2). E 2 -induced phosphorylation of Akt, was first apparent at 10 min and maximal at 30 min. Simultaneously, E 2 -induced pERK1/2 was first apparent at 5-10 min and maximal at 30 min. Inhibition of PI3K completely blocked E 2 activation of pAkt at 10 and 30 min and blocked E 2 activation of ERK1/2 at 10 min, which revealed a PI3K-independent activation of ERK at 30 min. Double immunocytochemical labeling for pERK1/2 and pAkt demonstrated that E 2 induced both signaling pathways in the same neurons. These results indicate a unified signaling mechanism for rapid E 2 action that leads to the coordinated activation of both pERK1/2 and pAkt in the same population of neurons. Implications of these results for understanding estrogen mechanism of action in neurons and therapeutic development are considered.

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“…bcl-2 overexpression increases expression of neural differentiation-associated genes through the TrkA/MEK/ERK pathway (64). Neuroprotection by transforming growth factor-␤1 involves activation of NF-B through the Akt/protein kinase B and ERK1/2 signaling pathways, further supporting that NF-B is a target of ERK signaling (65).…”

Section: Fig 7 Effect Of Erk Inhibition On Increased Nf-b Activationmentioning

confidence: 95%

Bcl-2 Attenuation of Oxidative Cell Death Is Associated with Up-regulation of γ-Glutamylcysteine Ligase via Constitutive NF-κB Activation

Jang¹,

Surh

2004

Journal of Biological Chemistry

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Oxidative stress induced by reactive oxygen intermediates often causes cell death via apoptosis, which is regulated by many functional genes and their protein products. The evolutionarily conserved protein Bcl-2 blocks apoptosis induced by a wide array of death signals. Despite extensive research, the molecular milieu that characterizes the anti-apoptotic function of Bcl-2 has not been fully clarified. In this work, we have inves-

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Neuroprotection by transforming growth factor-β1 involves activation of nuclear factor-κB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1,2 signaling pathways

Cited by 146 publications

References 50 publications

TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival

TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival

Estrogen Receptor Protein Interaction with Phosphatidylinositol 3-Kinase Leads to Activation of Phosphorylated Akt and Extracellular Signal-Regulated Kinase 1/2 in the Same Population of Cortical Neurons: A Unified Mechanism of Estrogen Action

Bcl-2 Attenuation of Oxidative Cell Death Is Associated with Up-regulation of γ-Glutamylcysteine Ligase via Constitutive NF-κB Activation

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