title: Caveolin-1 Expression Ameliorates Nephrotic Damage in a Rabbit Model of Cholesterol-Induced Hypercholesterolemia.
abstract: 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% (P < 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.
authors.affiliation: Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.|Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Lin
authors.affiliation: Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.|Graduate Institute of Integrative Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.|Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Vascular and Genomic Center, Changhua Christian Hospital, Changhua, Taiwan.|Department of Internal Medicine, Division of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan.|Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shih-Li
authors.initials: SL
authors.lastname: Su
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D002784:Cholesterol / Q000009:adverse effects*; D021984:Cyclophilin A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004579:Electron Transport / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000975:Antioxidants; D051242:Caveolin 1; D010455:Peptides; D017382:Reactive Oxygen Species; D002784:Cholesterol; D021984:Cyclophilin A