scholarly journals Neuroprotective Effects of B-Type Cinnamon Procyanidin Oligomers on MPP+-Induced Apoptosis in a Cell Culture Model of Parkinson’s Disease

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6422
Author(s):  
Qi Xu ◽  
Ziyu Chen ◽  
Borong Zhu ◽  
Yiming Li ◽  
Manju B. Reddy ◽  
...  

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP+)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP+. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP+. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP+ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Qi Xu ◽  
Anumantha G. Kanthasamy ◽  
Huajun Jin ◽  
Manju B. Reddy

Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis.Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD.Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration.Results. Hepcidin knockdown (32.3%,P<0.0001) upregulated ferroportin 1 expression and significantly (P<0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05) and DNA fragmentation by 29% (P=0.086) and increased cell viability by 22% (P<0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05) and intracellular iron by 28% (P<0.01), indicating the role of hepcidin in oxidative stress.Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.


2016 ◽  
Vol 16 (9) ◽  
pp. 1190-1197 ◽  
Author(s):  
Dziugas Meskelevicius ◽  
Kastytis Sidlauskas ◽  
Ruta Bagdonaviciute ◽  
Julius Liobikas ◽  
Daiva Majiene

Toxics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 94
Author(s):  
Soisungwan Satarug ◽  
Scott H. Garrett ◽  
Seema Somji ◽  
Mary Ann Sens ◽  
Donald A. Sens

We explored the potential role of zinc (Zn) and zinc transporters in protection against cytotoxicity of cadmium (Cd) in a cell culture model of human urothelium, named UROtsa. We used real-time qRT-PCR to quantify transcript levels of 19 Zn transporters of the Zrt-/Irt-like protein (ZIP) and ZnT gene families that were expressed in UROtsa cells and were altered by Cd exposure. Cd as low as 0.1 µM induced expression of ZnT1, known to mediate efflux of Zn and Cd. Loss of cell viability by 57% was seen 24 h after exposure to 2.5 µM Cd. Exposure to 2.5 µM Cd together with 10–50 µM Zn prevented loss of cell viability by 66%. Pretreatment of the UROtsa cells with an inhibitor of glutathione biosynthesis (buthionine sulfoximine) diminished ZnT1 induction by Cd with a resultant increase in sensitivity to Cd cytotoxicity. Conversely, pretreatment of UROtsa cells with an inhibitor of DNA methylation, 5-aza-2’-deoxycytidine (aza-dC) did not change the extent of ZnT1 induction by Cd. The induced expression of ZnT1 that remained impervious in cells treated with aza-dC coincided with resistance to Cd cytotoxicity. Therefore, expression of ZnT1 efflux transporter and Cd toxicity in UROtsa cells could be modulated, in part, by DNA methylation and glutathione biosynthesis. Induced expression of ZnT1 may be a viable mechanistic approach to mitigating cytotoxicity of Cd.


2014 ◽  
Vol 369 (1652) ◽  
pp. 20130502 ◽  
Author(s):  
Mu Li ◽  
Emily Zeringer ◽  
Timothy Barta ◽  
Jeoffrey Schageman ◽  
Angie Cheng ◽  
...  

Exosomes are tiny vesicles (30–150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer.


2021 ◽  
Vol 20 (2) ◽  
pp. 253-258
Author(s):  
Xiaomin Huang ◽  
Miao Huo

As an alternative to the use of narcotics, generally refractory to long-term effectiveness, for the management of neuropathic pain, we have explored the utility of senkyunolide I. Senkyunolide I is one of the bioactive components isolated from Ligusticum chuanxiong Hort known to exhibit multiple biological activities. In this study, we report senkyunolide I inhibition of chronic constriction injury induced neuropathic pain. Mechanistically, senkyunolide I inhibited chronic constriction injury induced apoptosis and the activity of microglia via extracellular signal regulated kinase pathway. We therefore suggest that senkyunolide I could serve as a promising drug for the treatment of neuropathic pain.


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