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Astaxanthin improves stem cell potency via an increase in the proliferation of neural progenitor cells.

Kim JH, Nam SW, Kim BW, Choi W, Lee JH, Kim WJ, Choi YH - Int J Mol Sci (2010)

Bottom Line: Treatment with astaxanthin significantly increased proliferation and colony formation of NPCs.In Western blot analysis, astaxanthin induced significant activation of phosphatidylinositol 3-kinase (PI3K) and its downstream mediators in a time-dependent manner.These results clearly showed that astaxanthin induces proliferation of NPCs via activation of the PI3K and MEK signaling pathways and improves stem cell potency via stemness acting signals.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterial Control, Dong-Eui University, Busan, 614-714, Korea; E-Mails: 12845@deu.ac.kr (J.-H.K.); bwkim@deu.ac.kr (B.-W.K.); wbchoi@deu.ac.kr (W.C.); jonghwanlee@deu.ac.kr (J.-H.L.).

ABSTRACT
The present study was designed to investigate the question of whether or not astaxanthin improves stem cell potency via an increase in proliferation of neural progenitor cells (NPCs). Treatment with astaxanthin significantly increased proliferation and colony formation of NPCs. For identification of possible activated signaling molecules involved in active cell proliferation occurring after astaxanthin treatment, total protein levels of several proliferation-related proteins, and expression levels of proliferation-related transcription factors, were assessed in NPCs. In Western blot analysis, astaxanthin induced significant activation of phosphatidylinositol 3-kinase (PI3K) and its downstream mediators in a time-dependent manner. Results of RT-PCR analysis showed upregulation of proliferation-related transcription factors and stemness genes. To estimate the relevance of PI3K and mitogen-activated protein, or extracellular signal-regulated kinase kinase (MEK) signaling pathways in cell growth of astaxanthin-treated NPCs, inhibition assays were performed with LY294002, a specific inhibitor of PI3K, and PD98059, a specific inhibitor of MEK, respectively. These results clearly showed that astaxanthin induces proliferation of NPCs via activation of the PI3K and MEK signaling pathways and improves stem cell potency via stemness acting signals.

Show MeSH
Astaxanthin induces active expression of several functional genes and stemness genes, and proliferation-related signal proteins in NPCs. (A) Astaxanthin induced upregulation of proliferation-related transcription factors (Rex1, CDK1, and CDK2), coupled with overexpression of stemness genes (OCT4, SOX2, Nanog, and KLF4); (B) Astaxanthin induced significant activation of PI3K and its downstream mediators, p-Rac, p-c-Raf, p-MEK, p-ERK, p-Akt, p-mTOR, and p-Stat3 in a time-dependent manner.
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f2-ijms-11-05109: Astaxanthin induces active expression of several functional genes and stemness genes, and proliferation-related signal proteins in NPCs. (A) Astaxanthin induced upregulation of proliferation-related transcription factors (Rex1, CDK1, and CDK2), coupled with overexpression of stemness genes (OCT4, SOX2, Nanog, and KLF4); (B) Astaxanthin induced significant activation of PI3K and its downstream mediators, p-Rac, p-c-Raf, p-MEK, p-ERK, p-Akt, p-mTOR, and p-Stat3 in a time-dependent manner.

Mentions: In both control NPCs and astaxanthin-treated cells, expression of molecular markers, including proliferation-related transcription factors and stemness genes, was assessed via RT-PCR. As shown in Figure 2A, 10 ng/mL astaxanthin applied for three days significantly induced upregulation of proliferation-related transcription factors (Rex1, CDK1, and CDK2), coupled with overexpression of stemness genes (OCT4, SOX2, Nanog, and KLF4) [25,26]. In particular, Rex1 expression was markedly increased in astaxanthin-treated cells. This result revealed that Rex1 expression is closely associated with proliferation of NPCs. In a recent study, we showed that Rex1 is a major gene, the expression of which is closely associated with proliferation of adipose tissue stromal cells [27]. Our present results are consistent with a recent report in which enhancement of Rex1 expression caused increased efficiency of cell proliferation. According to a recent report, four transcription factors (Oct4, Sox2, Klf4, and c-Myc) have been shown to reprogram primary mouse fibroblasts in culture [28]. Also, a balance between Klf4 and c-Myc is, in all likelihood, necessary for stable reprogramming in induced pluripotent stem cells [28]. In this study, astaxanthin-treated NPCs were shown to overexpress not only Oct4, Sox2, Nanog, and Rex1, but also Klf4 for the acquisition of active self-renewal activity (Figure 2A). Therefore, these results show that astaxanthin can induce active cell proliferation and that it improves stem cell potency in NPCs via stemness acting signals.


Astaxanthin improves stem cell potency via an increase in the proliferation of neural progenitor cells.

Kim JH, Nam SW, Kim BW, Choi W, Lee JH, Kim WJ, Choi YH - Int J Mol Sci (2010)

Astaxanthin induces active expression of several functional genes and stemness genes, and proliferation-related signal proteins in NPCs. (A) Astaxanthin induced upregulation of proliferation-related transcription factors (Rex1, CDK1, and CDK2), coupled with overexpression of stemness genes (OCT4, SOX2, Nanog, and KLF4); (B) Astaxanthin induced significant activation of PI3K and its downstream mediators, p-Rac, p-c-Raf, p-MEK, p-ERK, p-Akt, p-mTOR, and p-Stat3 in a time-dependent manner.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100832&req=5

f2-ijms-11-05109: Astaxanthin induces active expression of several functional genes and stemness genes, and proliferation-related signal proteins in NPCs. (A) Astaxanthin induced upregulation of proliferation-related transcription factors (Rex1, CDK1, and CDK2), coupled with overexpression of stemness genes (OCT4, SOX2, Nanog, and KLF4); (B) Astaxanthin induced significant activation of PI3K and its downstream mediators, p-Rac, p-c-Raf, p-MEK, p-ERK, p-Akt, p-mTOR, and p-Stat3 in a time-dependent manner.
Mentions: In both control NPCs and astaxanthin-treated cells, expression of molecular markers, including proliferation-related transcription factors and stemness genes, was assessed via RT-PCR. As shown in Figure 2A, 10 ng/mL astaxanthin applied for three days significantly induced upregulation of proliferation-related transcription factors (Rex1, CDK1, and CDK2), coupled with overexpression of stemness genes (OCT4, SOX2, Nanog, and KLF4) [25,26]. In particular, Rex1 expression was markedly increased in astaxanthin-treated cells. This result revealed that Rex1 expression is closely associated with proliferation of NPCs. In a recent study, we showed that Rex1 is a major gene, the expression of which is closely associated with proliferation of adipose tissue stromal cells [27]. Our present results are consistent with a recent report in which enhancement of Rex1 expression caused increased efficiency of cell proliferation. According to a recent report, four transcription factors (Oct4, Sox2, Klf4, and c-Myc) have been shown to reprogram primary mouse fibroblasts in culture [28]. Also, a balance between Klf4 and c-Myc is, in all likelihood, necessary for stable reprogramming in induced pluripotent stem cells [28]. In this study, astaxanthin-treated NPCs were shown to overexpress not only Oct4, Sox2, Nanog, and Rex1, but also Klf4 for the acquisition of active self-renewal activity (Figure 2A). Therefore, these results show that astaxanthin can induce active cell proliferation and that it improves stem cell potency in NPCs via stemness acting signals.

Bottom Line: Treatment with astaxanthin significantly increased proliferation and colony formation of NPCs.In Western blot analysis, astaxanthin induced significant activation of phosphatidylinositol 3-kinase (PI3K) and its downstream mediators in a time-dependent manner.These results clearly showed that astaxanthin induces proliferation of NPCs via activation of the PI3K and MEK signaling pathways and improves stem cell potency via stemness acting signals.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomaterial Control, Dong-Eui University, Busan, 614-714, Korea; E-Mails: 12845@deu.ac.kr (J.-H.K.); bwkim@deu.ac.kr (B.-W.K.); wbchoi@deu.ac.kr (W.C.); jonghwanlee@deu.ac.kr (J.-H.L.).

ABSTRACT
The present study was designed to investigate the question of whether or not astaxanthin improves stem cell potency via an increase in proliferation of neural progenitor cells (NPCs). Treatment with astaxanthin significantly increased proliferation and colony formation of NPCs. For identification of possible activated signaling molecules involved in active cell proliferation occurring after astaxanthin treatment, total protein levels of several proliferation-related proteins, and expression levels of proliferation-related transcription factors, were assessed in NPCs. In Western blot analysis, astaxanthin induced significant activation of phosphatidylinositol 3-kinase (PI3K) and its downstream mediators in a time-dependent manner. Results of RT-PCR analysis showed upregulation of proliferation-related transcription factors and stemness genes. To estimate the relevance of PI3K and mitogen-activated protein, or extracellular signal-regulated kinase kinase (MEK) signaling pathways in cell growth of astaxanthin-treated NPCs, inhibition assays were performed with LY294002, a specific inhibitor of PI3K, and PD98059, a specific inhibitor of MEK, respectively. These results clearly showed that astaxanthin induces proliferation of NPCs via activation of the PI3K and MEK signaling pathways and improves stem cell potency via stemness acting signals.

Show MeSH