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  • Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. 15111235

    We characterized undifferentiated (UN) and three differentiation conditions of the SH-SY5Y neuroblastoma cell line for phenotypic markers of dopaminergic cells, sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium ion (MPP+), the requirement to utilize the dopamine (DA) transporter (DAT) for MPP+ toxicity, and the neuroprotective effects of pramipexole. Cells were differentiated with retinoic acid (RA), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and RA followed by TPA (RA/TPA). RA/TPA treated cells exhibited the highest levels of tyrosine hydroxylase and DAT but lower levels of vesicular monoamine transporter. The kinetics of [3H]DA uptake and [3H]MPP+ uptake to DAT in RA/TPA differentiated cells were similar to that of rat and mouse caudate-putamen synaptosomes. RA/TPA differentiated cells evidenced high sensitivity to the neurotoxic effects of MPP+ (0.03 to 3.0 mM), and the neurotoxic effects of MPP+ were blocked with the DAT inhibitor 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909). DA-induced cell death was not more sensitive in RA vs RA/TPA differentiated cells and was not inhibited by transporter inhibitors. RA/TPA differentiated cells exhibited 3-fold and 6-fold higher levels, respectively, of DA D2 and D3 receptors than UN or RA differentiated cells. Pretreatment with pramipexole was protective against MPP+ in the RA/TPA differentiated cells but not in undifferentiated or RA differentiated cells. The neuroprotective effect of pramipexole was concentration-dependent and dopamine D2/D3 receptor dependent. In contrast, protection by pramipexole against DA was not DA receptor dependent. Further characterization of the neuroprotective effects of DA agonists in this model system can provide unique information about DA receptor dependent and independent mechanisms of neuroprotection.
    Document Type:
    Reference
    Product Catalog Number:
    AB1558
    Product Catalog Name:
    Anti-Dopamine D2 Receptor Antibody

  • Coagulation factors, fibrinogen and plasminogen activator inhibitor-1, are differentially regulated by yellow fever virus infection of hepatocytes. 23639427

    Yellow fever virus (YFV) infection poses a great risk to un-vaccinated individuals living or traveling in the endemic regions of Africa and South America. It is estimated that approximately 30,000 people die each year of this disease. The liver is the main target of YFV, where as many as 80% of the hepatocytes may become involved in the infection. The overwhelming infection of the liver is associated with the observed hemorrhagic disease manifestations such as petechiae, ecchymoses, and hematemesis which are all thought to be linked with the observed coagulation abnormalities that include prolonged clotting times, reduction in clotting factors, fibrin-split products (D-dimers) and elevated prothrombin times. Many factors involved in the coagulation pathway are produced by hepatocytes, such as fibrinogen (FBG) and plasminogen activator inhibitor-1 (PAI-1). Both of these proteins have been indicated in another flavivirus related disease, dengue, as having roles related to the bleeding abnormalities observed and overall outcome of infection. In this study we wanted to determine if FBG and PAI-1 expression levels by human hepatocytes was disrupted or altered by infection with either wild-type Asibi or vaccine strain17-D YFVs. Our findings indicate that YFV infection does affect the transcriptional and translational expression of FBG and PAI-1 in human hepatocytes and that these results are further affected by IL-6 during early stages of infection. These results may lead to further understanding of the molecular mechanism associated with bleeding abnormalities observed during late stage YFV infection.
    Document Type:
    Reference
    Product Catalog Number:
    HCVD3MAG-67K
    Product Catalog Name:
    MILLIPLEX MAP Human Cardiovascular Disease (Acute Phase) Magnetic Bead Panel 3 - Cardiovascular Disease Multiplex Assay
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