Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation

Mouche, Sarah; Mkaddem, Sanae Ben; Wang, Wei; Katic, Masa; Tseng, Yu–Hua; Carnesecchi, Stéphanie; Steger, Klaus; Foti, Michelangelo; Meier, Christoph A.; Muzzin, Patrick; Kahn, C. Ronald; Ogier–Denis, Éric; Szántó, Ildikó

doi:10.1016/j.bbamcr.2007.03.003

Cited by 74 publications

(64 citation statements)

References 51 publications

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“…It was recently shown that Nox2 and Nox4 each compensate for the deficiency of the other in lung endothelial cells (37). Down-regulation of Nox4 expression is associated with adipocyte differentiation (38), and Nox4 has been proposed to act as a switch that controls the transition between proliferation and differentiation of preadipocytes (39). Our results now suggest that increasing the expression of Nox1 and Nox2 and decreasing the expression of Nox4 are characteristics of chondrogenesis.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Generated by NADPH Oxidase 2 and 4 Are Required for Chondrogenic Differentiation

Kim

Choi²,

Yoon

et al. 2010

Journal of Biological Chemistry

124

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Although generation of reactive oxygen species (ROS) by NADPH oxidases (Nox) is thought to be important for signal transduction in nonphagocytic cells, little is known of the role ROS plays in chondrogenesis. We therefore examined the possible contribution of ROS generation to chondrogenesis using both ATDC5 cells and primary chondrocytes derived from mouse embryos. The intracellular level of ROS was increased during the differentiation process, which was then blocked by treatment with the ROS scavenger N-acetylcysteine. Expression of Nox1 and Nox2 was increased upon differentiation of ATDC5 cells and primary mouse chondrocytes, whereas that of Nox4, which was relatively high initially, was decreased gradually during chondrogenesis. In developing limb, Nox1 and Nox2 were highly expressed in prehypertrophic and hypertrophic chondrocytes. However, Nox4 was highly expressed in proliferating chondrocytes and prehypertrophic chondrocytes. Depletion of Nox2 or Nox4 expression by RNA interference blocked both ROS generation and differentiation of ATDC5 cells, whereas depletion of Nox1 had no such effect. We also found that ATDC5 cells depleted of Nox2 or Nox4 underwent apoptosis. Further, inhibition of Akt phosphorylation along with subsequent activation of ERK was observed in the cells. Finally, depletion of Nox2 or Nox4 inhibited the accumulation of proteoglycan in primary chondrocytes. Taken together, our data suggest that ROS generated by Nox2 or Nox4 are essential for survival and differentiation in the early stage of chondrogenesis.

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Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Generated by NADPH Oxidase 2 and 4 Are Required for Chondrogenic Differentiation

Kim

Choi²,

Yoon

et al. 2010

Journal of Biological Chemistry

124

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“…NADPH oxidase acts as the source of ROS in MSCs, as evidenced by the observation that Nox4 was downregulated after the induction of differentiation. Also, Nox4 is downregulated in mature adipocytes (57,75). Nox4 thus plays a vital role in adipogenesis from MSCs.…”

Section: Role Of Ros In Multipotent Ascsmentioning

confidence: 99%

Roles of Reactive Oxygen Species in the Fate of Stem Cells

Chaudhari

Jang³

2014

Antioxidants & Redox Signaling

120

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Significance: Stem cells are characterized by the properties of self-renewal and the ability to differentiate into multiple cell types, and thus maintain tissue homeostasis. Reactive oxygen species (ROS) are a natural byproduct of aerobic metabolism and have roles in cell signaling. Regulation of ROS has a vital role in maintaining ''stemness'' and differentiation of the stem cells, as well as in progression of stem-cell-associated diseases. Recent Advances: As of late, much research has been done on the adverse effects of ROS in stem cells. However, recently it has become apparent that in some cases redox status of the stem cell does have a role in maintaining its identity as such. Both pluripotent and multipotent stem cell types have been reported to possess enzymatic and nonenzymatic mechanisms for detoxification of ROS and to correct oxidative damage to the genome as well as the proteome. Critical Issues: Although context dependent and somewhat varied among different stem cell types, the correlation seems to exist between antioxidant defense level and stem cell fate change (i.e., proliferation, differentiation, and death). Changes in stem cell redox regulation may affect the pathogenesis of various human diseases. Future Directions: Dissecting the defined roles of ROS in distinct stem cell types will greatly enhance their basic and translational applications. Here, we discuss the various roles of ROS in adult, embryonic, and induced pluripotent stem cells.

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“…3B). Because expression of Nox family can be regulated by external stimuli such as hypoxia and insulin treatment [35][36][37], we investigated whether hypoxia modulates mRNA expression of Nox family. However, hypoxia (2% O 2 for 4 and 24 h) did not change the mRNA expression of Nox4, Nox5, and Duox1 in ASCs (Fig.…”

Section: Different Expression Of Nox Family Members Under Hypoxiamentioning

confidence: 99%

“…Of them, Nox4 is predominantly expressed in ASCs and functions as a switch between proliferation and differentiation of ASCs [34]. Nox4 modulates and generates ROS in insulin signaling and the expression of Nox4 is downregulated in the adipogenic differentiation of ASCs [35,36]. Although it has been known about the essential role of Nox4 in the adipogenic differentiation of ASCs, the Nox4-mediated stimulatory effect on ASCs has not been explored yet.…”

Section: Introductionmentioning

confidence: 99%

Primary Involvement of NADPH Oxidase 4 in Hypoxia-Induced Generation of Reactive Oxygen Species in Adipose-Derived Stem Cells

Kim

Song

Park

et al. 2012

Stem Cells and Development

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We have previously demonstrated that hypoxia stimulates adipose-derived stem cells (ASCs) through the generation of reactive oxygen species (ROS). However, the precise mechanism involved in the ROS generation by ASCs is not well understood. We sought to investigate in this work: (1) which subtype of NADPH oxidase (Nox) is primarily expressed in ASCs; (2) where Nox4 is localized in ASCs; and (3) whether silencing of Nox4 attenuates hypoxia-enhanced function of ASC. We used 2¢,7¢-dichlorofluorescin diacetate (DCF-DA) as an indicator of ROS generation and found that the fluorescence intensity of DCF-DA was significantly increased after hypoxia exposure (2% oxygen). In addition, hypoxia enhanced the proliferation and migration of ASCs and upregulated the mRNA expression of Oct4 and Rex1. Quantitative analysis of mRNA expression of Nox family in ASCs demonstrated that Nox4 is primarily expressed in ASCs, while immunofluorescence assay showed that Nox4 is mainly localized in the perinuclear region and overlaps with Mitotracker, a mitochondria marker. Silencing of Nox4 by siRNA treatment downregulated the RNA and protein expression of Nox4, which significantly reduced the ROS generation under hypoxia. In addition, Nox4 silencing significantly reduced the proliferation and migration of ASCs and downregulated the mRNA expression of Oct4 and Rex1. Phosphorylation of platelet-derived growth factor receptor-b, AKT, and ERK1/2 also diminished following Nox4 silencing. In a nutshell, these results suggest that Nox4 is primarily expressed in ASCs and plays a pivotal role in the hypoxia-enhanced stimulation of ASCs.

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Reduced expression of the NADPH oxidase NOX4 is a hallmark of adipocyte differentiation

Cited by 74 publications

References 51 publications

Reactive Oxygen Species Generated by NADPH Oxidase 2 and 4 Are Required for Chondrogenic Differentiation

Reactive Oxygen Species Generated by NADPH Oxidase 2 and 4 Are Required for Chondrogenic Differentiation

Roles of Reactive Oxygen Species in the Fate of Stem Cells

Primary Involvement of NADPH Oxidase 4 in Hypoxia-Induced Generation of Reactive Oxygen Species in Adipose-Derived Stem Cells

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