Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP+ intoxicated human neuroblastoma cells (SH-SY5Y)

Saravana Babu Chidambaram, Abid Bhat, Bipul Ray, Mani Sugumar, Serva Peddha Muthukumar, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Mohamed Musthafa Essa, Gilles J. Guillemin, Meena Kishore Sakharkar

Research output: Contribution to journalArticle

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Abstract

Polyphenols are shown to protect from or delay the progression of chronic neurodegenerative diseases. Mitochondrial dysfunction plays a key role in the pathogenesis of Parkinson’s disease (PD). This study was aims to gain insight into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma cells (SHSY5Y). The effects of cocoa on PPARγ, PGC1α, Nrf2 and TFAM protein expression and mitochondrial membrane potential were evaluated. A pre-exposure to cocoa extract decreased reactive oxygen species formation and restored mitochondrial membrane potential. The cocoa extract was found to up-regulate the expression of PPARγ and the downstream signalling proteins PGC1α, Nrf2 and TFAM. It increased the expression of the anti-apoptotic protein BCl2 and increased superoxide dismutase activity. Further, the cocoa extract down-regulated the expression of mitochondria fission 1 (Fis1) and up-regulated the expression of mitochondria fusion 2 (Mfn2) proteins, suggesting an improvement in mitochondrial functions in MPP+ intoxicated cells upon treatment with cocoa. Interestingly, cocoa up-regulates the expression of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. No change in the expression of PPARγ on treatment with cocoa extract was observed when the cells were pre-treated with PPARγ antagonist GW9662. This data suggests that cocoa mediates mitochondrial biogenesis via a PPARγ/PGC1α dependent signalling pathway and also has the ability to improve dopaminergic functions by increasing tyrosine hydroxylase expression. Based on our data, we propose that a cocoa bean extract and products thereof could be used as potential nutritional supplements for neuroprotection in PD.

Original languageEnglish
JournalNutritional Neuroscience
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Peroxisome Proliferator-Activated Receptors
Organelle Biogenesis
Neuroblastoma
Mitochondrial Membrane Potential
Tyrosine 3-Monooxygenase
Parkinson Disease
Mitochondria
Up-Regulation
Apoptosis Regulatory Proteins
Proteins
Catechin
Polyphenols
Neurodegenerative Diseases
Superoxide Dismutase
Reactive Oxygen Species
Dopamine
Chronic Disease
Enzymes

Keywords

  • Cocoa beans
  • Mitobiogenesis
  • MPP
  • Parkinsonism
  • PPARγ
  • SHSY5Y

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Neuroscience(all)
  • Nutrition and Dietetics

Cite this

Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP+ intoxicated human neuroblastoma cells (SH-SY5Y) . / Chidambaram, Saravana Babu; Bhat, Abid; Ray, Bipul; Sugumar, Mani; Muthukumar, Serva Peddha; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Mohamed Musthafa; Guillemin, Gilles J.; Sakharkar, Meena Kishore.

In: Nutritional Neuroscience, 01.01.2018.

Research output: Contribution to journalArticle

Chidambaram, Saravana Babu ; Bhat, Abid ; Ray, Bipul ; Sugumar, Mani ; Muthukumar, Serva Peddha ; Manivasagam, Thamilarasan ; Justin Thenmozhi, Arokiasamy ; Essa, Mohamed Musthafa ; Guillemin, Gilles J. ; Sakharkar, Meena Kishore. / Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP+ intoxicated human neuroblastoma cells (SH-SY5Y) In: Nutritional Neuroscience. 2018.
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abstract = "Polyphenols are shown to protect from or delay the progression of chronic neurodegenerative diseases. Mitochondrial dysfunction plays a key role in the pathogenesis of Parkinson’s disease (PD). This study was aims to gain insight into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma cells (SHSY5Y). The effects of cocoa on PPARγ, PGC1α, Nrf2 and TFAM protein expression and mitochondrial membrane potential were evaluated. A pre-exposure to cocoa extract decreased reactive oxygen species formation and restored mitochondrial membrane potential. The cocoa extract was found to up-regulate the expression of PPARγ and the downstream signalling proteins PGC1α, Nrf2 and TFAM. It increased the expression of the anti-apoptotic protein BCl2 and increased superoxide dismutase activity. Further, the cocoa extract down-regulated the expression of mitochondria fission 1 (Fis1) and up-regulated the expression of mitochondria fusion 2 (Mfn2) proteins, suggesting an improvement in mitochondrial functions in MPP+ intoxicated cells upon treatment with cocoa. Interestingly, cocoa up-regulates the expression of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. No change in the expression of PPARγ on treatment with cocoa extract was observed when the cells were pre-treated with PPARγ antagonist GW9662. This data suggests that cocoa mediates mitochondrial biogenesis via a PPARγ/PGC1α dependent signalling pathway and also has the ability to improve dopaminergic functions by increasing tyrosine hydroxylase expression. Based on our data, we propose that a cocoa bean extract and products thereof could be used as potential nutritional supplements for neuroprotection in PD.",
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AU - Bhat, Abid

AU - Ray, Bipul

AU - Sugumar, Mani

AU - Muthukumar, Serva Peddha

AU - Manivasagam, Thamilarasan

AU - Justin Thenmozhi, Arokiasamy

AU - Essa, Mohamed Musthafa

AU - Guillemin, Gilles J.

AU - Sakharkar, Meena Kishore

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