Shear stress influences spatial variations in vascular Mn-SOD expression: Implication for LDL nitration

Department of Biomedical Engineering and Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90089, USA.
AJP Cell Physiology (Impact Factor: 3.78). 06/2008; 294(6):C1576-85. DOI: 10.1152/ajpcell.00518.2007
Source: PubMed


Fluid shear stress modulates vascular production of endothelial superoxide anion (O2*-) and nitric oxide (*NO). Whether the characteristics of shear stress influence the spatial variations in mitochondrial manganese superoxide dismutase (Mn-SOD) expression in vasculatures is not well defined. We constructed a three-dimensional computational fluid dynamics model simulating spatial variations in shear stress at the arterial bifurcation. In parallel, explants of arterial bifurcations were sectioned from the human left main coronary bifurcation and right coronary arteries for immunohistolocalization of Mn-SOD expression. We demonstrated that Mn-SOD staining was prominent in the pulsatile shear stress (PSS)-exposed and atheroprotective regions, but it was nearly absent in the oscillatory shear stress (OSS)-exposed regions and lateral wall of arterial bifurcation. In cultured bovine aortic endothelial cells, PSS at mean shear stress (tau ave) of 23 dyn/cm2 upregulated Mn-SOD mRNA expression at a higher level than did OSS at tau ave = 0.02 dyn/cm2 +/- 3.0 and at 1 Hz (PSS by 11.3 +/- 0.4-fold vs. OSS by 5.0 +/- 0.5-fold vs. static condition; P < 0.05, n = 4). By liquid chromatography and tandem mass spectrometry, it was found that PSS decreased the extent of low-density lipoprotein (LDL) nitration, whereas OSS increased nitration (P < 0.05, n = 4). In the presence of LDL, treatment with Mn-SOD small interfering RNA increased intracellular nitrotyrosine level (P < 0.5, n = 4), a fingerprint for nitrotyrosine formation. Our findings indicate that shear stress in the atheroprone versus atheroprotective regions regulates spatial variations in mitochondrial Mn-SOD expression with an implication for modulating LDL nitration.

Download full-text


Available from: Rongsong Li,
  • Source
    • "(6) Tyrosine nitration is also involved in the cardiovascular system and related diseases. For example, nitroproteins have been indentified in ischemia reperfusion injury (Liu et al., 2009; Chen et al., 2008; Tao et al., 2013), vascular (Ai et al., 2008), and mouse heart (Bigelow & Qian, 2008; Zhang et al., 2010). (7) Tyrosine nitration is involved in kidney disease. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress plays important roles in a wide range of diseases such as cancer, inflammatory disease, neurodegenerative disorders, etc. Tyrosine nitration in a protein is a chemically stable oxidative modification, and a marker of oxidative injuries. Mass spectrometry (MS) is a key technique to identify nitrotyrosine-containing proteins and nitrotyrosine sites in endogenous and synthetic nitroproteins and nitropeptides. However, in vivo nitrotyrosine-containing proteins occur with extreme low-abundance to severely challenge the use of MS to identify in vivo nitroproteins and nitrotyrosine sites. A preferential enrichment of nitroproteins and/or nitropeptides is necessary before MS analysis. Current enrichment methods include immuno-affinity techniques, chemical derivation of the nitro group plus target isolations, followed with tandem mass spectrometry analysis. This article reviews the MS techniques and pertinent before-MS enrichment techniques for the identification of nitrotyrosine-containing proteins. This article reviews future trends in the field of nitroproteomics, including quantitative nitroproteomics, systems biological networks of nitroproteins, and structural biology study of tyrosine nitration to completely clarify the biological functions of tyrosine nitration. © 2013 Wiley Periodicals, Inc. Mass Spec Rev.
    Mass Spectrometry Reviews 12/2013; 34(4). DOI:10.1002/mas.21413 · 7.71 Impact Factor
  • Source
    • "After exposure for ten weeks, the heart tissues of mice were dissected and paraffin blocks were made. The heart sections were stained with anti-GSH antibody (1:100) (Virogen) for visualizing protein S-glutathionylation with standard immunohistochemistry procedure as described previously [27] "
    [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter < 200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production.
    Biochemical and Biophysical Research Communications 06/2013; 436(3). DOI:10.1016/j.bbrc.2013.05.127 · 2.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fluid shear stress is intimately involved in vascular oxidative stress and atherosclerosis. Oxidative stress induces molecular signaling that regulates the development of vascular calcification. The explants of New Zealand White (NZW) rabbit aortas were used to assess vascular oxidative stress in non-obstructive, albeit inflammatory, lesions. The development of Micro-Electro-Mechanical Systems (MEMS) shear stress and oxidative stress sensors has provided a means to study atherogenic hemodynamics and vascular oxidative stress. Computational fluid dynamics and Doppler ultrasound were utilized in combination with the immunohistochemistry staining to show that the flow disturbance as assessed by the micro-scale sensors in non-obstructive plaques was associated with oxidative stress relevant for initiation of the arterial plaque. Our findings represent a concerted effort to assess the relationship between oxidative stress and the mechanically unstable plaque in the presence of vascular calcification.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:6557-9. DOI:10.1109/IEMBS.2009.5334502
Show more