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Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits

Caveolins are an essential component of cholesterol-rich invaginations of the plasma membrane known as caveolae. These flask-shaped, invaginated structures participate in a number of important cellular processes, including vesicular transport, cholesterol homeostasis, and signal transduction. We inv...

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Autores principales: Chen, Ya-Hui, Lin, Wei-Wen, Liu, Chin-San, Hsu, Li-Sung, Lin, Yueh-Min, Su, Shih-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901645/
https://www.ncbi.nlm.nih.gov/pubmed/24475013
http://dx.doi.org/10.1371/journal.pone.0071862
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author Chen, Ya-Hui
Lin, Wei-Wen
Liu, Chin-San
Hsu, Li-Sung
Lin, Yueh-Min
Su, Shih-Li
author_facet Chen, Ya-Hui
Lin, Wei-Wen
Liu, Chin-San
Hsu, Li-Sung
Lin, Yueh-Min
Su, Shih-Li
author_sort Chen, Ya-Hui
collection PubMed
description Caveolins are an essential component of cholesterol-rich invaginations of the plasma membrane known as caveolae. These flask-shaped, invaginated structures participate in a number of important cellular processes, including vesicular transport, cholesterol homeostasis, and signal transduction. We investigated the effects of CAV-1 on mitochondrial biogenesis and antioxidant enzymes in hypercholesterolemia-affected target organs. A total of eighteen male New Zealand white rabbits were divided into three groups: a normal-diet group, an untreated hypercholesterolemia-induced group, and a hypercholesterolemia-induced group that received intravenous administration of antennapedia-CAV-1 (AP-CAV-1) peptide every 2 days for 2 weeks. Serum biochemistry, CAV-1 distribution, neutral lipid distribution, mitochondrial morphology, biogenesis-mediated protein content, oxidative stress balance, antioxidant enzyme levels, and apoptotic cell death of liver tissue were analysed. Hepatic and circulating cholesterol and low-density lipoprotein cholesterol (LDL-C) levels differed significantly between the three groups (P<0.05). Immunohistochemical staining intensity of CAV-1 was greater in AP-CAV-1-treated rabbits than in untreated rabbits, especially in the vicinity of the liver vasculature. The high levels of neutral lipids, malondialdehyde, peroxisome proliferator-activated receptor-γ coactive 1α (PGC-1α), and nuclear respiratory factor-1 (NRF-1) seen in untreated hypercholesteremic animals were attenuated by administration of AP-CAV-1 (P<0.05). In addition, mitochondria in animals that received treatment exhibited darker electron-dense matrix and integrated cristae. Furthermore, the levels of ROS modulator 1 (Romo1) and superoxide dismutase (SOD)-2, as well as catalase activity were significantly lower in CAV-1-treated hypercholesterolemic rabbits (P<0.05). AP-CAV-1 treatment also restored mitochondrial respiratory chain subunit protein content (OXPHOS complexes I–V), thereby preserving mitochondrial function (P<0.05). Furthermore, AP-CAV-1 treatment significantly suppressed apoptotic cell death, as evidenced by a reduction in the number of TUNEL-positive cells. Our results indirectly indicate that CAV-1 mediates the negative effects of PGC-1α on hepatic mitochondrial respiratory chain function, promotes the antioxidant enzyme defence system, and maintains mitochondrial biogenesis.
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spelling pubmed-39016452014-01-28 Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits Chen, Ya-Hui Lin, Wei-Wen Liu, Chin-San Hsu, Li-Sung Lin, Yueh-Min Su, Shih-Li PLoS One Research Article Caveolins are an essential component of cholesterol-rich invaginations of the plasma membrane known as caveolae. These flask-shaped, invaginated structures participate in a number of important cellular processes, including vesicular transport, cholesterol homeostasis, and signal transduction. We investigated the effects of CAV-1 on mitochondrial biogenesis and antioxidant enzymes in hypercholesterolemia-affected target organs. A total of eighteen male New Zealand white rabbits were divided into three groups: a normal-diet group, an untreated hypercholesterolemia-induced group, and a hypercholesterolemia-induced group that received intravenous administration of antennapedia-CAV-1 (AP-CAV-1) peptide every 2 days for 2 weeks. Serum biochemistry, CAV-1 distribution, neutral lipid distribution, mitochondrial morphology, biogenesis-mediated protein content, oxidative stress balance, antioxidant enzyme levels, and apoptotic cell death of liver tissue were analysed. Hepatic and circulating cholesterol and low-density lipoprotein cholesterol (LDL-C) levels differed significantly between the three groups (P<0.05). Immunohistochemical staining intensity of CAV-1 was greater in AP-CAV-1-treated rabbits than in untreated rabbits, especially in the vicinity of the liver vasculature. The high levels of neutral lipids, malondialdehyde, peroxisome proliferator-activated receptor-γ coactive 1α (PGC-1α), and nuclear respiratory factor-1 (NRF-1) seen in untreated hypercholesteremic animals were attenuated by administration of AP-CAV-1 (P<0.05). In addition, mitochondria in animals that received treatment exhibited darker electron-dense matrix and integrated cristae. Furthermore, the levels of ROS modulator 1 (Romo1) and superoxide dismutase (SOD)-2, as well as catalase activity were significantly lower in CAV-1-treated hypercholesterolemic rabbits (P<0.05). AP-CAV-1 treatment also restored mitochondrial respiratory chain subunit protein content (OXPHOS complexes I–V), thereby preserving mitochondrial function (P<0.05). Furthermore, AP-CAV-1 treatment significantly suppressed apoptotic cell death, as evidenced by a reduction in the number of TUNEL-positive cells. Our results indirectly indicate that CAV-1 mediates the negative effects of PGC-1α on hepatic mitochondrial respiratory chain function, promotes the antioxidant enzyme defence system, and maintains mitochondrial biogenesis. Public Library of Science 2014-01-24 /pmc/articles/PMC3901645/ /pubmed/24475013 http://dx.doi.org/10.1371/journal.pone.0071862 Text en © 2014 Chen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chen, Ya-Hui
Lin, Wei-Wen
Liu, Chin-San
Hsu, Li-Sung
Lin, Yueh-Min
Su, Shih-Li
Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits
title Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits
title_full Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits
title_fullStr Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits
title_full_unstemmed Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits
title_short Caveolin-1 Provides Palliation for Adverse Hepatic Reactions in Hypercholesterolemic Rabbits
title_sort caveolin-1 provides palliation for adverse hepatic reactions in hypercholesterolemic rabbits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901645/
https://www.ncbi.nlm.nih.gov/pubmed/24475013
http://dx.doi.org/10.1371/journal.pone.0071862
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