Inhibitory effect of green tea extract on β-amyloid-induced PC12 cell death by inhibition of the activation of NF-κB and ERK/p38 MAP kinase pathway through antioxidant mechanisms

Lee, Sun Young; Lee, Jae Woong; Lee, Heesoon; Yoo, Hyung Sik; Yun, Yong Soo; Oh, Ki Wan; Ha, Tae Youl; Hong, Jin Tae

doi:10.1016/j.molbrainres.2005.07.009

Cited by 92 publications

(48 citation statements)

References 53 publications

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“…These systems have been implicated in Aβ-induced neuronal cell death in vitro [116]. Mice pre-treated orally for three weeks with 1.5 mg/ kg or 3 mg/kg EGCG showed dose-dependent improvement of all these pathological effects [115].…”

Section: Intracerebroventricular Injections Of Aβ42mentioning

confidence: 98%

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

Attar

Rahimi

Bitan

2013

Translational Neuroscience

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Abnormal protein folding and self-assembly causes over 30 cureless human diseases for which no diseasemodifying therapies are available. The common side to all these diseases is formation of aberrant toxic protein oligomers and amyloid fibrils. Both types of assemblies are drug targets, yet each presents major challenges to drug design, discovery, and development. In this review, we focus on two small molecules that inhibit formation of toxic amyloid protein assemblies -the green-tea derivative (-)-epigallocatechin-3-gallate (EGCG), which was identified through a combination of epidemiologic data and a compound library screen, and the molecular tweezer CLR01, whose inhibitory activity was discovered in our group based on rational reasoning, and subsequently confirmed experimentally. Both compounds act in a manner that is not specific to one particular protein and thus are useful against a multitude of amyloidogenic proteins, yet they act via distinct putative mechanisms. CLR01 disrupts protein aggregation through specific binding to lysine residues, whereas the mechanisms underlying the activity of EGCG are only recently beginning to unveil. We discuss current in vitro and, where available, in vivo literature related to EGCG and CLR01's effects on amyloid β-protein, α-synuclein, transthyretin, islet amyloid polypeptide, and calcitonin. We also describe the toxicity, pharmacokinetics, and mechanism of action of each compound.

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Section: Intracerebroventricular Injections Of Aβ42mentioning

confidence: 98%

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

Attar

Rahimi

Bitan

2013

Translational Neuroscience

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“…It can also be activated by ROS (12,(18)(19)(20)(21). Previous studies have demonstrated that p38MAPK activation is implicated in neuronal damage associated with ischemia and neurodegenerative disease (32), and it is one of the apoptotic markers during PC12 cell death induced by a variety of stimuli (15)(16)(17)(18). In the present study, we found that exposure of PC12 cells to CoCl 2 significantly upregulated expression of p-p38MAPK and that pretreatment of cells with SB203580, an inhibitor of p38MAPK, markedly blocked CoCl 2 -induced neuronal injuries, indicating that activation of p38MAPK mediates neuronal damage induced by CoCl 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Zou et al reported that CoCl 2 activates caspase-3 and p38 mitogen-activated protein kinase (MAPK), which are involved in CoCl 2 -induced apoptosis in PC12 cells (4). p38MAPK has been demonstrated to be one of the apoptotic markers during PC12 cell death induced by various stimuli (15)(16)(17)(18). Notably, excessive ROS have been shown to activate members of MAPKs, including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK) and p38MAPK in various types of cells (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells

et al. 2011

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Abstract. The present study investigated whether there is an interaction between reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) during chemical hypoxia-induced injury in PC12 cells. The results of the present study showed that cobalt chloride (CoCl 2 ), a chemical hypoxia agent, markedly induced ROS generation and phosphorylation of p38MAPK, as well as neuronal injuries. N-acetylcysteine (NAC), a ROS scavenger, blocked CoCl 2 -induced phosphorylation of p38MAPK. In addition, SB203580, an inhibitor of p38MAPK attenuated not only CoCl 2 -induced activation of p38MAPK, but also ROS production. These results suggest that ROS and p38MAPK are capable of interacting positively during chemical hypoxia. Furthermore, NAC and SB203580 markedly prevented CoCl 2 -induced cytotoxicity, apoptosis and a loss of mitochondrial membrane potential. Taken together, our findings suggest that the positive interaction between CoCl 2 induction of ROS and p38MAPK activation may play a significant role in CoCl 2 -induced neuronal injuries. We provide new insights into the mechanisms responsible for CoCl 2 -induced injuries in PC12 cells.

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“…Another biochemical parameter, activation of MAP kinase transduction pathways, is widely used to monitor cellular responses to exogenous agents that might affect the cell intracellularly (42)(43)(44)(45). N2A and BE(2)-M17 cells were treated with the inhibitors RRGC, RRGL, RRGI, and CRGC and incubated (37°C, 5% CO 2 ) for 30 and 60 min at which time the cells were fixed and then assessed using an in cell Western assay.…”

Section: Tetrapeptide Inhibitors Of Botulinum Neurotoxinmentioning

confidence: 99%

Basic Tetrapeptides as Potent Intracellular Inhibitors of Type A Botulinum Neurotoxin Protease Activity

Ahmed¹

2010

J Anal Bioanal Techniques

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Botulinum neurotoxins (BoNT) are the most potent of all toxins that cause flaccid muscle paralysis leading to death. They are also potential biothreat agents. A systematic investigation of various short peptide inhibitors of the BoNT protease domain with a 17-residue peptide substrate led to argininearginine-glycine-cysteine having a basic tetrapeptide structure as the most potent inhibitor. When assayed in the presence of dithiothreitol (DTT), the inhibitory effect was drastically reduced. Replacing the terminal cysteine with one hydrophobic residue eliminated the DTT effect but with two hydrophobic residues made the pentapeptide a poor inhibitor. Replacing the first arginine with cysteine or adding an additional cysteine at the N terminus did not improve inhibition. When assessed using mouse brain lysates, the tetrapeptides also inhibited BoNT/A cleavage of the endogenous SNAP-25. The peptides penetrated the neuronal cell lines, N2A and BE(2)-M17, without adversely affecting metabolic functions as measured by ATP production and P-38 phosphorylation. Biological activity of the peptides persisted within cultured chick motor neurons and rat and mouse cerebellar neurons for more than 40 h and inhibited BoNT/A protease action inside the neurons in a dose-and time-dependent fashion. Our results define a tetrapeptide as the smallest peptide inhibitor in the backdrop of a large substrate protein of 200؉ amino acids having multiple interaction regions with its cognate enzyme. The inhibitors should also be valuable candidates for drug development. Botulinum neurotoxins (BoNT)2 produced by strains of Clostridium botulinum, are the deadliest of all toxins (1). There are seven distinct serotypes, A-F, of which BoNT/A afflicts humans most frequently. The latter is also the most stable in neurons causing long term paralysis. The toxins are 150-kDa proteins comprising a 50-kDa protease light chain (LC) and a 100-kDa binding-translocating heavy chain. Upon entry to animal body, the toxins travel to peripheral neurons where heavy chain binds and translocates LC into the neurons. After dissociating from the heavy chain (2), LC cleaves at specific sites on one of three SNARE (soluble N-ethylmaleimide factor attachment protein receptor) proteins, thereby blocking exocytosis of acetylcholine into the neuromuscular junction and causing muscle paralysis. The paralysis prevents normal respiration and eventually leads to death of the animal. One of the hallmark features of BoNT/A intoxication is the extreme persistence of symptoms with neuroparalysis often lasting in excess of 3-4 months. Currently, there is no effective postexposure therapeutic available against botulism. Because of extreme toxicity, BoNT is a potential biowarfare and bioterrorism threat, and both Centers for Disease Control and Prevention and the United States Department of Agriculture have placed it as a category A threat agent.The substrate for BoNT/A is an ϳ210-residue SNAP-25 depending on species. Schmidt and Bostian (3) reported that unlike most other proteases,...

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Inhibitory effect of green tea extract on β-amyloid-induced PC12 cell death by inhibition of the activation of NF-κB and ERK/p38 MAP kinase pathway through antioxidant mechanisms

Cited by 92 publications

References 53 publications

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells

Basic Tetrapeptides as Potent Intracellular Inhibitors of Type A Botulinum Neurotoxin Protease Activity

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