Oncotarget

Research Papers:

Cavin-1 regulates caveolae-mediated LDL transcytosis: crosstalk in an AMPK/eNOS/ NF-κB/Sp1 loop

Xiang-Li Bai, Xiao-Yan Yang, Ju-Yi Li, Ye Li, Xiong Jia, Zhi-Fan Xiong, Yu-Mei Wang and Si Jin _

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Oncotarget. 2017; 8:103985-103995. https://doi.org/10.18632/oncotarget.21944

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Abstract

Xiang-Li Bai1,2, Xiao-Yan Yang3, Ju-Yi Li3, Ye-Li3, Xiong Jia1, Zhi-Fan Xiong1, Yu-Mei Wang5 and Si Jin1,3,4

1Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China

2Department of Clinical Laboratory, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China

3Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China

4Department of Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China

5Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China

Correspondence to:

Si Jin, email: [email protected]

Keywords: cavin-1; low density lipoprotein transcytosis; nitric oxide

Received: May 01, 2017     Accepted: September 05, 2017     Published: October 19, 2017

ABSTRACT

Caveolae are specialized lipid rafts structure in the cell membrane and critical for regulating endothelial functions, e.g. transcytosis of macromolecules like low density lipoprotein (LDL) etc. Specifically, the organization and functions of caveolae are mediated by structure protein (caveolin-1) and adapter protein (cavin-1). The pathogenic role of caveolin-1 is well studied; nevertheless, mechanisms whereby cavin-1 regulates signaling transduction remain poorly understood. The aim of this study was designed to explore the role of cavin-1 in caveolae-mediated LDL transcytosis across endothelial cells. We reported here that cavin-1 knockdown mediated by small interfering RNA (siRNA) caused a significant decrease of LDL transcytosis. Moreover, cavin-1 knockdown increased the activity of endothelial nitric oxide synthase (eNOS) and the production of nitric oxide (NO). Consequently, an eNOS inhibitor, N-Nitro-L-Arginine Methyl Ester (L-NAME), not only suppressed the activity of specificity protein (Sp1) and nuclear factor kappa B (NF-κB), but also inhibited both activities via activating adenosine 5‘-monophosphate- activated protein kinase (AMPK). In conclusion, we proposed an AMPK/eNOS/NF-κB/Sp1 circuit loop was formed to regulate caveolae residing proteins’ expression, e.g. LDL receptor (LDLR), caveolin-1, eNOS, thereby to regulate caveolae-mediated LDL transcytosis in endothelial cells.


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