Induction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cells

Cho, Yoon Mi; Jang, Yong Suk; Jang, Young Min; Chung, Shin; Kim, Ho Shik; Lee, Jeong Hwa; Jeong, Seong Whan; Kim, In Kyung; Kim, Jung Jin; Kim, Kwang S.; Kwon, Oh Joo

doi:10.3858/emm.2009.41.6.049

Cited by 54 publications

(51 citation statements)

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“…[27][28][29][30][31] In particular, during myogenesis ER stress enhances myoblast differentiation and myofiber formation. 32 Cho et al 31 have shown that ER stress increases during ESC differentiation toward neural cells and that this differentiation is further enhanced through chemical treatment with the ER stress inducers, thapsigargin and tunicamycin. We demonstrated that Nrf3 localizes to the ER at different stages of differentiation ( Figure 6A) and Zhang et al 26 have demonstrated that ER chemical stressors in COS-1 cells activate Nrf3.…”

Section: Discussionmentioning

confidence: 99%

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

Pepe

Xiao²,

Zampetaki³

et al. 2010

Circulation Research

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Rationale: Nuclear factor erythroid 2-related factor (Nrf)3, a member of the cap 'N' collar family of transcription factors that bind to the DNA-antioxidant responsive elements, is involved in reactive oxygen species balancing and in muscle precursor migration during early embryo development. Objective: To investigate the functional role of Nrf3 in smooth muscle cell (SMC) differentiation in vitro and in vivo. Methods and Results: Nrf3 was upregulated significantly following 1 to 8 days of SMC differentiation. Knockdown of Nrf3 resulted in downregulation of smooth muscle specific markers expression, whereas enforced expression of Nrf3 enhanced SMC differentiation in a dose-dependent manner. SMC-specific transcription factor myocardin, but not serum response factor, was significantly upregulated by Nrf3 overexpression. Strikingly, the binding of SRF and myocardin to the promoter of smooth muscle differentiation genes was dramatically increased by Nrf3 overexpression, and Nrf3 can directly bind to the promoters of SMC differentiation genes as demonstrated by chromatin immunoprecipitation assay. Moreover, NADPH-derived reactive oxygen species production during SMC differentiation was further enhanced by Nrf3 overexpression through upregulation of NADPH oxidase and inhibition of antioxidant signaling pathway. In addition, Nrf3 was involved in the endoplasmic reticulum stressor induced SMC differentiation. (SMCs). [1][2][3] Our previous studies showed that growth factor stimulation, 2 mechanical force or extracellular matrix 4 can be used to drive ESC differentiation toward the vascular lineage. We have established an in vitro model for ESC differentiation into SMCs, 3 which involves the choice of extracellular matrix protein collagen IV, 3,5,6 to investigate SMC differentiation more closely. In the adult organism, SMCs have the main physiological function of contracting and controlling the blood vessel tone, diameter, blood pressure and blood flow. In response to vascular injury, SMCs dramatically increase their rate of proliferation, migration and synthetic capacity. 7,8 Atherosclerosis and postangioplasty restenosis, for example, are characterized by the development of an enlarged neointima. 9 The cells responsible for the neointima formation have been identified as not only SMC migrating from the tunica media, 10 but also vascular progenitors that originate from the circulation and the perivascular adventitia, which differentiate into vascular SMCs in the lesion. 11-14 However, the mechanisms involved in SMC differentiation in vitro and in vivo is still poorly understood.In a microarray screen for factors involved in vascular progenitor differentiation, we identified nuclear factor erythroid 2-related factor (Nrf)3 expression to be constantly modulated. Nrf3 is the most recently identified member of the Nrf family and contains a domain homologous to the cap 'N' collar (CNC) transcription factors. 15 The CNC domain is a unique, conserved region, located at the amino-terminus of the bZIP domain. 16 Nrf3 heterodim...

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Section: Discussionmentioning

confidence: 99%

Crucial Role of Nrf3 in Smooth Muscle Cell Differentiation From Stem Cells

Pepe

Xiao²,

Zampetaki³

et al. 2010

Circulation Research

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show abstract

“…ER stress, accumulation of unfolded protein in the endoplasmic reticulum, can be provoked primarily by imbalance in homeostasis, proteasome activity during degeneration and differentiation (Kozutsumi et al, 1988;Wong et al, 1993;Friedlander et al, 2000;Cho et al, 2009). ER stress induces an adaptive signaling pathway called the UPR that involves activation of transcription factors, XBP-1 and activating transcription factor 6 (ATF6) (Yoshida et al, 2000;Lee et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice

et al. 2010

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“…ER stress activates specific signaling pathways (Breckenridge et al, 2003;Schroder and Kaufman, 2005), in a process known as the unfolded protein response (Kaufman, 1999;Malhotra and Kaufman, 2007;Cho et al, 2009), which includes phosphorylation of eukaryotic initiation factor 2α (eIF2α) by the activated PKR-like endoplasmic reticulum kinase (PERK) Boyce et al, 2005), cleavage of the X-box binding protein-1 (XBP-1) mRNA by the activated inositol-requiring enzyme 1, which translocates to the nucleus and regulates expression of ER chaperone genes, such as glucose-regulated protein 78 (GRP78) (Tirasophon et al, 1998;Calfon et al, 2002), and cleavage of activating transcription factor 6 (ATF6) by proteases, such as S1P and S2P in the Golgi, which regulates expression of ER stress-target genes, such as C/EBP homologous protein (CHOP) and XBP-1 (Yoshida et al, 2001).…”

Section: Introductionmentioning

confidence: 99%