Abstract
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.
Highlights
Caveolae are omega-shaped invaginations of the plasma membrane with a diameter of approximately 50–100 nm
Blood glucose and cholesterol levels were significantly higher in untreated hypercholesterolemic rabbits and in caveolin-1-treated rabbits (CAV-1 group) than in rabbits that received a diet of normal rat chow
We found that the expression levels of proteins related to mitochondrial biogenesis (PGC-1 a, 230.8%; nuclear respiratory factor-1 (NRF-1), 223.5%) and anti-oxidation (SOD2, 235.3%; CAT, 28.3%) were significantly lower in the AP-CAV-1-treated group than in the untreated control group (P,0.05)
Summary
Caveolae are omega-shaped invaginations of the plasma membrane with a diameter of approximately 50–100 nm These flask-shaped, invaginated structures participate in a number of important cellular processes including vesicular transport, cholesterol homeostasis, signal transduction and tumour suppression [1,2]. Found that caveolin-1-deficient (CAV-1 2/2) mice exhibited enhanced plasma triglyceride (TG) levels, increased high-density lipoprotein (HDL) levels, and reduced hepatic very low-density lipoprotein (VLDL) secretion. They found that caveolin-1 deficiency prevented transcytosis of LDL across endothelial cells, suggesting that CAV-1 may be implicated in the regulation of plasma LDL levels and, may play an important role in the development of atherosclerosis [2]. Studies have shown that CAV-1 negatively regulates endothelial nitric oxide synthase (eNOS), the enzyme responsible for synthesizing nitric oxide [4,17,18,19]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.