Browsing by Author "Du, Nicole"

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    Author Correction: Salt-dependent Blood Pressure in Human Aldosterone Synthase-Transgenic Mice
    (Springer Nature, 2018-10-25) Gu, Huiying; Ma, Zhizhong; Wang, Jian; Zhu, Timothy; Du, Nicole; Shatara, Adam; Yi, Xin; Kowala, Mark C.; Du, Yansheng; Neurology, School of Medicine
    A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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    Pb Induces MCP-1 in the Choroid Plexus
    (MDPI, 2022-02) Gu, Huiying; Xu, Yundan; Du, Nicole; Yu, Yongqi; Zheng, Wei; Du, Yansheng; Neurology, School of Medicine
    Lead (Pb) is an environmental element that has been implicated in the development of dementia and Alzheimer’s disease (AD). Additionally, innate immune activation contributes to AD pathophysiology. However, the mechanisms involved remain poorly understood. The choroid plexus (CP) is not only the site of cerebrospinal fluid (CSF) production, but also an important location for communication between the circulation and the CSF. In this study, we investigated the involvement of the CP during Pb exposure by evaluating the expression of the monocyte chemoattractant protein-1 (MCP-1). MCP-1 is highly expressed in the CP compared to other CNS tissues. MCP-1 regulates macrophage infiltration and is upregulated in AD brains. Our study revealed that Pb exposure stimulated MCP-1 expression, along with a significantly increased macrophage infiltration into the CP. By using cultured Z310 rat CP cells, Pb exposure stimulated MCP-1 expression in a dose-related fashion and markedly activated both NF-κB and p38 MAP kinase. Interestingly, both SB 203580, a p38 inhibitor, and BAY 11-7082, an NF-κB p65 inhibitor, significantly blocked Pb-induced MCP-1 expression. However, SB203580 did not directly inhibit NF-κB p65 phosphorylation. In conclusion, Pb exposure stimulates MCP-1 expression via the p38 and NF-κB p65 pathways along with macrophage infiltration into the CP.
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    Salt-dependent Blood Pressure in Human Aldosterone Synthase-Transgenic Mice
    (Springer Nature, 2017-03-28) Gu, Huiying; Ma, Zhizhong; Wang, Jian; Zhu, Timothy; Du, Nicole; Shatara, Adam; Yi, Xin; Kowala, Mark C.; Du, Yansheng; Department of Neurology, IU School of Medicine
    Hypertension is one of the most important, preventable causes of premature morbidity and mortality in the developed world. Aldosterone is a major mineralocorticoid hormone that plays a key role in the regulation of blood pressure and is implicated in the pathogenesis of hypertension and heart failure. Aldosterone synthase (AS, cytochrome P450 11B2, cyp11B2) is the sole enzyme responsible for the production of aldosterone in humans. To determine the effects of increased expression of human aldosterone synthase (hAS) on blood pressure (BP), we established transgenic mice carrying the hAS gene (cyp11B2). We showed that hAS overexpression increased levels of aldosterone in hAS+/− mice. On high salt diet (HS), BPs of hAS+/− mice were significantly increased compared with WT mice. Fadrozole (an inhibitor of aldosterone synthase) treatment significantly reduced BPs of hAS+/− mice on HS. This is the first time overexpression of AS in a transgenic mouse line has shown an ability to induce HP. Specifically inhibiting AS activity in these mice is a promising therapy for reducing hypertension. This hAS transgenic mouse model is therefore an ideal animal model for hypertension therapy studies.