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Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.

Phan CW, David P, Wong KH, Naidu M, Sabaratnam V - PLoS ONE (2015)

Bottom Line: An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated.Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells.MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells.

View Article: PubMed Central - PubMed

Affiliation: Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.

ABSTRACT
Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.

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Related in: MedlinePlus

The effects of mushroom extracts and compounds on neurite outgrowth of differentiating N2a cells by using (a) quantification of neurite bearing cells, and (b) chromogenic method at optical density 562.NGF (50 ng/mL) was used as a positive control. Values are mean ± SD from three independent experiments. Different alphabets represent significant differences between samples (p < 0.05).
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pone.0143004.g002: The effects of mushroom extracts and compounds on neurite outgrowth of differentiating N2a cells by using (a) quantification of neurite bearing cells, and (b) chromogenic method at optical density 562.NGF (50 ng/mL) was used as a positive control. Values are mean ± SD from three independent experiments. Different alphabets represent significant differences between samples (p < 0.05).

Mentions: The mean value of neurite-bearing cells in NGF treated cells (positive control) was 22.67 ± 0.74% as shown in Fig 2. The aqueous and ethanol extracts of the P. giganteus (20 μg/mL) caused a significant (p < 0.05) increase in neurite-bearing cells by 4.0- and 4.7-times when compared to the control cells with medium only. P-coumaric, cinnamic, and oleic acids (100 μM) caused little or no neuritogenic effects on differentiating N2a cells, i.e. 8.56 ± 1.51%, 10.17 ± 1.88%, 10.06 ± 1.32%; respectively. Linoleic acid caused 20.78 ± 2.43% of N2a cells to bear neurites. Uridine (100 μM) stimulated the highest (p < 0.05) percentage of neurite-bearing cell (43.09 ± 4.88%), which was 1.9-times higher than that of the positive control.


Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying Mechanism.

Phan CW, David P, Wong KH, Naidu M, Sabaratnam V - PLoS ONE (2015)

The effects of mushroom extracts and compounds on neurite outgrowth of differentiating N2a cells by using (a) quantification of neurite bearing cells, and (b) chromogenic method at optical density 562.NGF (50 ng/mL) was used as a positive control. Values are mean ± SD from three independent experiments. Different alphabets represent significant differences between samples (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643974&req=5

pone.0143004.g002: The effects of mushroom extracts and compounds on neurite outgrowth of differentiating N2a cells by using (a) quantification of neurite bearing cells, and (b) chromogenic method at optical density 562.NGF (50 ng/mL) was used as a positive control. Values are mean ± SD from three independent experiments. Different alphabets represent significant differences between samples (p < 0.05).
Mentions: The mean value of neurite-bearing cells in NGF treated cells (positive control) was 22.67 ± 0.74% as shown in Fig 2. The aqueous and ethanol extracts of the P. giganteus (20 μg/mL) caused a significant (p < 0.05) increase in neurite-bearing cells by 4.0- and 4.7-times when compared to the control cells with medium only. P-coumaric, cinnamic, and oleic acids (100 μM) caused little or no neuritogenic effects on differentiating N2a cells, i.e. 8.56 ± 1.51%, 10.17 ± 1.88%, 10.06 ± 1.32%; respectively. Linoleic acid caused 20.78 ± 2.43% of N2a cells to bear neurites. Uridine (100 μM) stimulated the highest (p < 0.05) percentage of neurite-bearing cell (43.09 ± 4.88%), which was 1.9-times higher than that of the positive control.

Bottom Line: An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated.Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells.MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells.

View Article: PubMed Central - PubMed

Affiliation: Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.

ABSTRACT
Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus (linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine) were tested for neurite outgrowth activity. Uridine (100 μM) was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma (N2a) cells by 43.1 ± 0.5%, which was 1.8-fold higher than NGF (50 ng/mL)-treated cells. Uridine which was present in P. giganteus (1.80 ± 0.03 g/100g mushroom extract) increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Further, phosphorylation of the mammalian target of rapamycin (mTOR) was also increased. MEK/ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein (CREB) and expression of growth associated protein 43 (GAP43); all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.

Show MeSH
Related in: MedlinePlus