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:	Ya-Hui Chen, Wei-Wen Lin, Chin-San Liu, Li-Sung Hsu, Yueh-Min Lin, Shih-Li Su
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b597d39ead2b4e328e2f9883c79d1fdc
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spelling	oai:doaj.org-article:b597d39ead2b4e328e2f9883c79d1fdc2021-11-18T08:35:57ZCaveolin-1 provides palliation for adverse hepatic reactions in hypercholesterolemic rabbits.1932-620310.1371/journal.pone.0071862https://doaj.org/article/b597d39ead2b4e328e2f9883c79d1fdc2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24475013/?tool=EBIhttps://doaj.org/toc/1932-6203Caveolins 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.Ya-Hui ChenWei-Wen LinChin-San LiuLi-Sung HsuYueh-Min LinShih-Li SuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e71862 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ya-Hui Chen Wei-Wen Lin Chin-San Liu Li-Sung Hsu Yueh-Min Lin Shih-Li Su Caveolin-1 provides palliation for adverse hepatic reactions in hypercholesterolemic rabbits.
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.
format	article
author	Ya-Hui Chen Wei-Wen Lin Chin-San Liu Li-Sung Hsu Yueh-Min Lin Shih-Li Su
author_facet	Ya-Hui Chen Wei-Wen Lin Chin-San Liu Li-Sung Hsu Yueh-Min Lin Shih-Li Su
author_sort	Ya-Hui Chen
title	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_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_sort	caveolin-1 provides palliation for adverse hepatic reactions in hypercholesterolemic rabbits.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b597d39ead2b4e328e2f9883c79d1fdc
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Caveolin-1 provides palliation for adverse hepatic reactions in hypercholesterolemic rabbits.

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