Ca2+-mediated Mitochondrial Reactive Oxygen Species Metabolism Augments Wnt/β-Catenin Pathway Activation to Facilitate Cell Differentiation

Rharass, Tareck; Lemcke, Heiko; Lantow, Margaréta; Kuznetsov, Sergei A.; Weiss, Dieter G.; Panàkovà, Daniela

doi:10.1074/jbc.m114.573519

Cited by 91 publications

(134 citation statements)

References 51 publications

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“…Rharass and colleagues demonstrated that the primary trigger for neuronal differentiation upon growth factor depletion in human neural progenitor cells is the generation of mROS. Interestingly, they reported that after growth factor depletion mROS reached a maximum increase of ~200% at 1 h and this increase was significantly but not completely restored at 3 h (no further time points were tested) [24]. Results from Xavier and colleagues are in agreement with our findings, also reporting a transient increase in superoxide mROS 1 h after the induction of NSC differentiation [27].…”

Section: Discussionsupporting

confidence: 82%

“…Notably, our data is in accordance with other processes reported to occur at early stages of ROS-induced NSC differentiation, namely Dvl dissociation and β-catenin activation [24].…”

Section: Discussionsupporting

confidence: 81%

“…Free Dvl is then capable of activating the Wnt/β-catenin signaling pathway that, among other effects, is known to induce the transcription of neurogenic genes [23]. During the process of NSC neuronal differentiation, Dvl2 was also reported to dissociate from NRX [24]. Accordingly, our coimmunoprecipitation studies confirmed that 60 sec of laser exposure induces the dissociation of the Dvl2:NRX complex 1 h after treatment (Fig.…”

Section: Ros Activate β-Catenin Through the Dissociation Of Dvl2 Fromsupporting

confidence: 71%

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Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

et al. 2017

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Section: Discussionsupporting

confidence: 82%

“…Notably, our data is in accordance with other processes reported to occur at early stages of ROS-induced NSC differentiation, namely Dvl dissociation and β-catenin activation [24].…”

Section: Discussionsupporting

confidence: 81%

Section: Ros Activate β-Catenin Through the Dissociation Of Dvl2 Fromsupporting

confidence: 71%

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Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

et al. 2017

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“…32,33 Treatment of S34F-expressing cells with the NOX1/4-specific inhibitor GKT137831 or with the pan-NOX inhibitor DPI profoundly reduced ASC oligomerization and thereby NLRP3 inflammasome assembly; thus, NLRP3 activation in response to SGMs is NOX1/4 dependent ( Figure 7B). Moreover, elevated levels of ROS in U2AF1-S34F cells were abrogated by GKT137831 or DPI treatment ( Figure 7N-O).…”

Section: Org Frommentioning

confidence: 99%

“…[32][33][34][35][36] Thus, we hypothesized that ROS generated by either S100A9 or somatic gene mutations (SGMs) would direct activation of b-catenin in MDSs. In accordance with this, the mean percentage of ROS positive cells was increased 16.5-fold in MDS BM-MNCs (n 5 5) compared with normal donors (n 5 2) (P 5 .011) ( Figure 6A), with corresponding significant increases in ROS MFI (P 5 .028) ( Figure 6B).…”

Section: S100a9 and Mds Sgms Trigger Pyroptosis And B-catenin Activatmentioning

confidence: 99%

The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype

Basiorka¹,

McGraw²,

Eksioglu³

et al. 2016

Blood

295

350

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Key Points• Key biological features of MDSs are explained by NLRP3 inflammasome activation, which drives pyroptotic cell death and b-catenin activation.• Alarmin signals and founder gene mutations license this redox-sensitive inflammasome platform.Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1b (IL-1b) and IL-18, and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPCs and bone marrow plasma. Further, like somatic gene mutations, S100A9-induced signaling activates NADPH oxidase (NOX), increasing levels of reactive oxygen species (ROS) that initiate cation influx, cell swelling, and b-catenin activation. Notably, knockdown of NLRP3 or caspase-1, neutralization of S100A9, and pharmacologic inhibition of NLRP3 or NOX suppress pyroptosis, ROS generation, and nuclear b-catenin in MDSs and are sufficient to restore effective hematopoiesis. Thus, alarmins and founder gene mutations in MDSs license a common redox-sensitive inflammasome circuit, which suggests new avenues for therapeutic intervention. (Blood. 2016;128(25):2960-2975

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Nanoscale Optoregulation of Neural Stem Cell Differentiation by Intracellular Alteration of Redox Balance

Hassanpour-Tamrin

Taheri

Hasani-Sadrabadi

et al. 2017

Adv Funct Materials

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Regulation of stem cell (SC) fate, a decision between self-renewal and differentiation, is of immense importance in regenerative medicine and has been proven to be a powerful stimulus regulating many cell functions influencing the SC fate. This study uses triphenylphosphonium-functionalized gold nanoparticles (TPP-AuNPs) to explore the interplay of intracellular electromagnetic (EM) exposure and the SC fate. Localized EM waves are generated inside neural stem cells (NSCs) to stimulate TPP-AuNPs (AuNPs), targeting the mitochondria through inducing reactive oxygen species and differentiating these cells into neurons. Following laser irradiation of TPP-AuNPs-transfected NSCs, their differentiation to neurons is monitored by tracing the relevant markers both at the genetic and protein levels. The electrophysiology technique is further used to examine the functionality of neurons. The results confirm that TPP-AuNPs subjected to electromotive forces have the potential to regulate cellular fate, although further investigations are still required to shed light on the mechanisms underlying the interaction of EM-stimulated TPP-AuNPs on cellular fate to design highly adjustable cell differentiation and reprogramming methods.

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Ca2+-mediated Mitochondrial Reactive Oxygen Species Metabolism Augments Wnt/β-Catenin Pathway Activation to Facilitate Cell Differentiation

Cited by 91 publications

References 51 publications

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

Blue light potentiates neurogenesis induced by retinoic acid-loaded responsive nanoparticles

The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype

Nanoscale Optoregulation of Neural Stem Cell Differentiation by Intracellular Alteration of Redox Balance

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