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Mechanistic basis for protection of differentiated SH-SY5Y cells by oryzanol-rich fraction against hydrogen peroxide-induced neurotoxicity.

Ismail N, Ismail M, Imam MU, Azmi NH, Fathy SF, Foo JB, Abu Bakar MF - BMC Complement Altern Med (2014)

Bottom Line: ORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis.The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kβ).These findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. norsharina@upm.edu.my.

ABSTRACT

Background: Apoptosis is often the end result of oxidative damage to neurons. Due to shared pathways between oxidative stress, apoptosis and antioxidant defence systems, an oxidative insult could end up causing cellular apoptosis or survival depending on the severity of the insult and cellular responses. Plant bioresources have received close attention in recent years for their potential role in regulating the pathways involved in apoptosis and oxidative stress in favour of cell survival. Rice bran is a bioactive-rich by-product of rice milling process. It possesses antioxidant properties, making it a promising source of antioxidants that could potentially prevent oxidative stress-induced neurodegenerative diseases.

Methods: Thus, the present study investigated the neuroprotective properties of oryzanol-rich fraction (ORF) against hydrogen peroxide (H2O2)-induced neurotoxicity in differentiated human neuroblastoma SH-SY5Y cells. ORF was extracted from rice bran using a green technology platform, supercritical fluid extraction system. Furthermore, its effects on cell viability, morphological changes, cell cycle, and apoptosis were evaluated. The underlying transcriptomic changes involved in regulation of oxidative stress, apoptosis and antioxidant defence systems were equally studied.

Results: ORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis. The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kβ).

Conclusion: These findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.

No MeSH data available.


Related in: MedlinePlus

Cell cycle analysis. Flow cytometric measurement of cell death and cell cycle on SH-SY5Y cells pretreated with Oryzanol-rich fraction (ORF) (100 μg/mL) before exposure to 250 μM H2O2 over 24 h. Results are mean ± SD. #p <0.05 versus control, *p <0.05 versus H2O2.
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Fig3: Cell cycle analysis. Flow cytometric measurement of cell death and cell cycle on SH-SY5Y cells pretreated with Oryzanol-rich fraction (ORF) (100 μg/mL) before exposure to 250 μM H2O2 over 24 h. Results are mean ± SD. #p <0.05 versus control, *p <0.05 versus H2O2.

Mentions: Figure 3 showed significant cell death (at Sub G1) (40% ± 5.88%) upon exposure to 250 μM H2O2 in comparison to untreated cells (8% ± 2.34%), p < 0.05. In contrast, pretreatment with 100 μg/mL ORF did not produce as much dead cells (14% ± 5.0%) as with H2O2 treatment alone, p < 0.05. In addition, there was no significant difference in cell populations at S and G2/M phases among control, H2O2 alone and ORF treatment.Figure 3


Mechanistic basis for protection of differentiated SH-SY5Y cells by oryzanol-rich fraction against hydrogen peroxide-induced neurotoxicity.

Ismail N, Ismail M, Imam MU, Azmi NH, Fathy SF, Foo JB, Abu Bakar MF - BMC Complement Altern Med (2014)

Cell cycle analysis. Flow cytometric measurement of cell death and cell cycle on SH-SY5Y cells pretreated with Oryzanol-rich fraction (ORF) (100 μg/mL) before exposure to 250 μM H2O2 over 24 h. Results are mean ± SD. #p <0.05 versus control, *p <0.05 versus H2O2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4528700&req=5

Fig3: Cell cycle analysis. Flow cytometric measurement of cell death and cell cycle on SH-SY5Y cells pretreated with Oryzanol-rich fraction (ORF) (100 μg/mL) before exposure to 250 μM H2O2 over 24 h. Results are mean ± SD. #p <0.05 versus control, *p <0.05 versus H2O2.
Mentions: Figure 3 showed significant cell death (at Sub G1) (40% ± 5.88%) upon exposure to 250 μM H2O2 in comparison to untreated cells (8% ± 2.34%), p < 0.05. In contrast, pretreatment with 100 μg/mL ORF did not produce as much dead cells (14% ± 5.0%) as with H2O2 treatment alone, p < 0.05. In addition, there was no significant difference in cell populations at S and G2/M phases among control, H2O2 alone and ORF treatment.Figure 3

Bottom Line: ORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis.The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kβ).These findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia. norsharina@upm.edu.my.

ABSTRACT

Background: Apoptosis is often the end result of oxidative damage to neurons. Due to shared pathways between oxidative stress, apoptosis and antioxidant defence systems, an oxidative insult could end up causing cellular apoptosis or survival depending on the severity of the insult and cellular responses. Plant bioresources have received close attention in recent years for their potential role in regulating the pathways involved in apoptosis and oxidative stress in favour of cell survival. Rice bran is a bioactive-rich by-product of rice milling process. It possesses antioxidant properties, making it a promising source of antioxidants that could potentially prevent oxidative stress-induced neurodegenerative diseases.

Methods: Thus, the present study investigated the neuroprotective properties of oryzanol-rich fraction (ORF) against hydrogen peroxide (H2O2)-induced neurotoxicity in differentiated human neuroblastoma SH-SY5Y cells. ORF was extracted from rice bran using a green technology platform, supercritical fluid extraction system. Furthermore, its effects on cell viability, morphological changes, cell cycle, and apoptosis were evaluated. The underlying transcriptomic changes involved in regulation of oxidative stress, apoptosis and antioxidant defence systems were equally studied.

Results: ORF protected differentiated SH-SY5Y cells against H2O2-induced neurotoxicity through preserving the mitochondrial metabolic enzyme activities, thus reducing apoptosis. The mechanistic basis for the neuroprotective effects of ORF included upregulation of antioxidant genes (catalase, SOD 1 and SOD 2), downregulation of pro-apoptotic genes (JNK, TNF, ING3, BAK1, BAX, p21 and caspase-9), and upregulation of anti-apoptotic genes (ERK1/2, AKT1 and NF-Kβ).

Conclusion: These findings suggest ORF may be an effective antioxidant that could prevent oxidative stress-induced neurodegenerative disorders.

No MeSH data available.


Related in: MedlinePlus