Generalized linear model to identify independent clinical variables associated with copy number and mtDNA∆Ct.

<p>TCA: tricyclic antidepressant.</p><p>SSRI: selective serotonin reuptake inhibitor.</p><p>SNRI: selective serotonin-norepinephrine inhibitor.</p><p>NaSSA: noradrenergic and specific serotonergic antidepressant.</p><p>BZDs: benzodiazepines.</p><p>Generalized linear model to identify independent clinical variables associated with copy number and mtDNA∆Ct.</p

Comparison of mtDNA copy number/per cell between normal controls and MDD patients.

<p>Comparison of mtDNA copy number/per cell between normal controls and MDD patients.</p

Demographic and clinical characteristics between comparison and MDD groups.

<p>BMI: body mass index.</p><p>TCA: tricyclic antidepressant.</p><p>SSRI: selective serotonin reuptake inhibitor.</p><p>SNRI: selective serotonin-norepinephrine inhibitor.</p><p>NaSSA: noradrenergic and specific serotonergic antidepressant.</p><p>BZDs: benzodiazepines.</p><p>IQR: interquartile range.</p><p>Demographic and clinical characteristics between comparison and MDD groups.</p

Comparison of mtDNA△Ct between normal controls and MDD patients.

<p>Comparison of mtDNA△Ct between normal controls and MDD patients.</p

Caveolin-1 Expression Ameliorates Nephrotic Damage in a Rabbit Model of Cholesterol-Induced Hypercholesterolemia

<div><p>Caveolin-1 (CAV-1) participates in regulating vesicular transport, signal transduction, tumor progression, and cholesterol homeostasis. In the present study, we tested the hypothesis that CAV-1 improves dyslipidemia, inhibits cyclophilin A (CypA)- mediated ROS production, prevents mitochondrial compensatory action and attenuates oxidative stress responses in cholesterol-induced hypercholesterolemia. To determine the role of CAV-1 in mediating oxidative and antioxidative as well as cholesterol homeostasis, hypercholesterolemic rabbits were intravenously administered antenapedia-CAV-1 (AP-CAV-1) peptide for 2 wk. AP-CAV-1 enhanced CAV-1 expression by ˃15%, inhibited CypA expression by ˃50% (<i>P</i> < 0.05) and significantly improved dyslipidemia, thus reducing neutral lipid peroxidation. Moreover, CAV-1 attenuated hypercholesterolemia-induced changes in mitochondrial morphology and biogenesis and preserved mitochondrial respiratory function. In addition, CAV-1 protected against hypercholesterol-induced oxidative stress responses by reducing the degree of oxidative damage and enhancing the expression of antioxidant enzymes. CAV-1 treatment significantly suppressed apoptotic cell death, as evidenced by the reduction in the number of terminal deoxynucleotidyl transferase dUTP nick end-labeling-positive cells. We concluded that CAV-1 plays a critical role in inhibiting CypA-mediated ROS production, improving dyslipidemia, maintaining mitochondrial function, and suppressing oxidative stress responses that are vital for cell survival in hypercholesterol-affected renal organs.</p></div

Changes in the mtDNA copy numbers in the control and CAV-1 groups.

<p>A significant decrease in mtDNA copy number/cell was observed in the CAV-1 group compared with the normal group by SigmaPlot <i>t</i>-tests (* <i>P<</i>0.05). Values are mean ± SD from at least 3 independent experiments, n = 6 for each group.</p

CAV-1 reduces inflammatory activity and then protects tubular nephrocalcinosis and pyelonephritis.

<p>(A) CAV-1 is well-distributed in the glomerulus (<i>upper</i>). Staining intensity was higher in the AP-CAV-1-treated rabbits (the HCAV-1 group) than in the untreated hypercholesterolemic rabbits (the HC group). CypA was expressed in the endothelial and smooth muscle cells of the renal vasculature (<i>lower</i>, arrows). CypA was significantly induced in the HC group. (B) Quantification of CAV-1 and CypA on immunohistochemical staining in rabbit renal tissue per 400× field for five fields per animal; <i>n</i> = 6 rabbits for each group, scale bar = 1 μm. (C) H&E-stained renal sections from extensive calcium salt in and around the renal tubules, and the inflammatory cell-infiltrated HC group (<i>middle</i>, magnification 400×, bar = 20 μm). The data represent at least three independent experiments; * and † differ significantly for the NC and HC groups, respectively, at <i>P</i> < 0.05.</p

CAV-1 enhances the Nrf2-mediated antioxidant defense system.

<p>(A) Staining intensity increased nuclear expression of Nfr2 (<i>upper</i>), reduced cytosolic expression of keap1 (<i>middle</i>), and increased cytosolic expression of GCLC (<i>lower</i>) significantly more in the HCAV-1 group than in the HC group. (B) Quantification of Nrf2, Keap1, and GCLC. The data represent at least three independent experiments; * and † differ significantly for the NC and HC groups, respectively, at <i>P</i> < 0.05 (magnification 400×, bar = 20 μm).</p

Serum biochemical data in experimental animals.¹

<p>Serum biochemical data in experimental animals.<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154210#t001fn001" target="_blank">¹</a></p

Characteristics of the experimental animals.

a<p>, Data are represented as mean ± SD obtained from three independent experiments, n = 6.</p>b<p>, Normal group: normal diet without any treatment; Control group: fed 2% cholesterol diet; Caveolin-1 group:</p><p>fed 2% cholesterol diet and treated with caveolin-1 peptide. TG, triglyceride; AST, aspartate aminotransferase; ALT, alanine transaminase; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; INSbay, insulin; FFA, free-fatty acid.</p><p>Data were analyzed by one-way ANOVA.</p>*<p>, p<0.05; the results was compared to the normal group.</p