Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liú, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R.; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

doi:10.14336/ad.2016.0117

Cited by 28 publications

(23 citation statements)

References 50 publications

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“…Additionally, endoplasmic reticulum (ER) stress seems to play a critical role in the progression of Parkinson’s disease. Results obtained by Cai et al [ 79 ] indicate that ER stress-induced apoptosis in PD might be inhibited by a basic fibroblast growth factor (bFGF). Administration of bFGF improved motor function recovery, increased tyrosine hydroxylase positive neuron survival, and upregulated the levels of neurotransmitters in the brain of a rat model of Parkinson’s disease.…”

Section: Introductionmentioning

confidence: 99%

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

Bohush

Niewiadomska

Filipek

2018

IJMS

117

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Parkinson’s disease (PD) is a neurodegenerative disorder caused by insufficient dopamine production due to the loss of 50% to 70% of dopaminergic neurons. A shortage of dopamine, which is predominantly produced by the dopaminergic neurons within the substantia nigra, causes clinical symptoms such as reduction of muscle mass, impaired body balance, akinesia, bradykinesia, tremors, postural instability, etc. Lastly, this can lead to a total loss of physical movement and death. Since no cure for PD has been developed up to now, researchers using cell cultures and animal models focus their work on searching for potential therapeutic targets in order to develop effective treatments. In recent years, genetic studies have prominently advocated for the role of improper protein phosphorylation caused by a dysfunction in kinases and/or phosphatases as an important player in progression and pathogenesis of PD. Thus, in this review, we focus on the role of selected MAP kinases such as JNKs, ERK1/2, and p38 MAP kinases in PD pathology.

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Section: Introductionmentioning

confidence: 99%

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

Bohush

Niewiadomska

Filipek

2018

IJMS

117

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“…It has been used as a therapeutic agent for the restoration and maintenance of neuronal function in both basic and clinical studies. Basic fibroblast growth factor (bFGF) is highly expressed in the nervous system and exerts multiple roles supporting the survival and growth of cultured neurons and neural stem cells [8][9][10]. Although bFGF and NGF have distinctive neuroprotective properties, their short half-life and rapid diffusion rate seriously hinders their clinical applicability.…”

Section: Introductionmentioning

confidence: 99%

Dual Delivery of bFGF- and NGF-Binding Coacervate Confers Neuroprotection by Promoting Neuronal Proliferation

Wang

Cai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are essential for proper development, survival, growth, and maintenance of neurons in the central and peripheral nervous systems. However, because bFGF and NGF have short half-life and rapid diffusion rate, they have limited clinical efficacy. Thus, there is an urgent need to develop an effective delivery system to protect bFGF and NGF from proteolysis while maintaining their normal bioactivities. Methods: To more efficiently deliver bFGF and NGF, we used a coacervate (synthesized with heparin and a biodegradable polycation at mass ratio of 500: 100). The maximal package loads of GFs in coacervate were determined by Western Blotting; release efficiency of bFGF and NGF was measured by ELISA. Additionally, we evaluated the effect of bFGF and NGF on the viability, survival, and proliferation of neurons by MTT assay, BrdU cell proliferation, and calcein staining. Results: Our coacervate incorporated bFGF and NGF and continuously released them for at least three weeks. This enhanced the growth and proliferation of PC12 cells and SH-SY5Y cells. Moreover, co-delivery of bFGF and NGF using coacervate was more neuroprotective than free application of both factors or coacervate delivery of each GF separately. Conclusions: Dual delivery of bFGF and NGF binding coacervate was neuroprotective via stimulating the growth and proliferation of neurons.

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“…Oxidative stress disrupts endoplasmic reticulum (ER) which is a key component of cellular protein homeostasis, controlling the regulation of protein trafficking, synthesis, folding, and degradation (Perri et al ., 2016 ). The implementing process in protein quality control in the ER is the unfolded protein response (UPR), which is activated upon ER stress to reestablish homeostasis through a sophisticated transcriptionally and translationally regulated signaling network (Hoozemans & Scheper, 2012 ; Cai et al ., 2016 ). Accumulation of misfolded proteins within the ER activates the UPR resulting in the execution of adaptive or non-adaptive signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, enormous efforts have been deployed to formulate new strategies that address neuronal degeneration. The latest studies indicated that mitochondrial dysfunction and ER-stress targeted regimens could be a potential approach to overcome neurodegeneration (Kondratyev et al ., 2007 ; Benyair et al ., 2011 ; Hoozemans & Scheper, 2012 ; Leitman et al ., 2013 ; Cai et al ., 2016 ; Ogen-Shtern et al ., 2016 ). Following this line of evidence, a few recent studies showed that some natural polyphenolic compounds exhibited neuroprotective effects by regulation of redox stress-mediated UPR response (Wu et al ., 2015 ; Cheng et al ., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Oleuropein and rutin protect against 6-OHDA-induced neurotoxicity in PC12 cells through modulation of mitochondrial function and unfolded protein response

Elmazoğlu

Ergin

Şahin

et al. 2017

Interdisciplinary Toxicology

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Parkinson’s disease (PD) is a highly prevalent neurodegenerative disorder, often associated with oxidative stress-induced transcriptional changes in dopaminergic neurons. Phenolic antioxidants, oleuropein (OLE) and rutin (RUT) have attracted a great interest due to their potential to counteract oxidative protein aggregation and toxicity. This study aimed at examining the effects of OLE and RUT against 6-OHDA-induced stress response in rat pheochromocytoma cells. When differentiated PC12 cells were exposed to oxidative stress composer 6-OHDA (100 μM, 8 h), a decreased mitochondrial membrane potential (ΔΨm) was observed along with a significant loss of cell viability and apoptotic nuclear changes. Exposure to 6-OHDA resulted in unfolded protein response (UPR) in differentiated PC12 cells as evidenced by an increased level of endoplasmic reticulum (ER)-localized transmembrane signal transducer IRE1α, adaptive response proteins ATF-4 and proapoptotic transcription factor CHOP. OLE or RUT pretreatment (24 h) at low doses (1–50 μM) protected the differentiated PC12 cells from 6-OHDA-induced cytotoxicity as assessed by increased viability, improved ΔΨm and inhibited apoptosis, whereas relatively high doses of OLE or RUT (>50 μM) inhibited cell growth and proliferation, indicating a typical hormetic effect. In hormetic doses, OLE and RUT up-regulated 6-OHDA-induced increase in IRE1α, ATF-4 and inhibited CHOP, PERK, BIP and PDI. 6-OHDA-activated XBP1 splicing was also inhibited by OLE or RUT. The presented results suggest that neuroprotection against 6-OHDA-induced oxidative toxicity may be attributable to neurohormetic effects of OLE or RUT at low doses through regulating mitochondrial functions, controlling persistent protein misfolding, activating and/or amplificating the adaptive response-related signaling pathways, leading to UPR prosurvival output.

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Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

Cited by 28 publications

References 50 publications

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

Role of Mitogen Activated Protein Kinase Signaling in Parkinson’s Disease

Dual Delivery of bFGF- and NGF-Binding Coacervate Confers Neuroprotection by Promoting Neuronal Proliferation

Oleuropein and rutin protect against 6-OHDA-induced neurotoxicity in PC12 cells through modulation of mitochondrial function and unfolded protein response

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