Cadmium Induces Vascular Endothelial Cell Detachment by Downregulating Claudin-5 and ZO-1 Levels

被引:1
作者
Hara, Takato [1 ]
Asatsu, Mayuka [1 ]
Yamagishi, Tatsuya [1 ]
Ohata, Chinami [1 ]
Funatsu, Hitomi [1 ]
Takahashi, Yuzuki [1 ]
Shirai, Misaki [1 ]
Nakata, Chiaki [1 ]
Katayama, Haruka [1 ]
Kaji, Toshiyuki [2 ]
Fujie, Tomoya [2 ]
Yamamoto, Chika [1 ]
机构
[1] Toho Univ, Fac Pharmaceut Sci, 2-2-1 Miyama, Funabashi, Chiba 2748510, Japan
[2] Tokyo Univ Sci, Fac Pharmaceut Sci, 2641 Yamazaki, Noda, Chiba 2788510, Japan
关键词
cadmium; vascular endothelial cell; tight junction; claudin-5; ZO-1; TIGHT JUNCTIONS; ZINC PROTECTION; MONOLAYER; CYTOTOXICITY; EXPOSURE; LEAD;
D O I
10.3390/ijms252011035
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cadmium is a contributing factor to cardiovascular diseases and highly toxic to vascular endothelial cells. It has a distinct mode of injury, causing the de-endothelialization of regions in the monolayer structure of endothelial cells in a concentration-dependent manner. However, the specific molecules involved in the cadmium toxicity of endothelial cells remain unclear. The purpose of this study was to identify the specific molecular mechanisms through which cadmium affects endothelial detachment. Cadmium inhibited the expression of claudin-5 and zonula occludens (ZO)-1, which are components of tight junctions (strongest contributors to intercellular adhesion), in a concentration- and time-dependent manner. Compared to arsenite, zinc, and manganese, only cadmium suppressed the expression of both claudin-5 and ZO-1 molecules. Moreover, the knockdown of claudin-5 and ZO-1 exacerbated cadmium-induced endothelial cell injury and expansion of the detachment area, whereas their overexpression reversed these effects. CRE-binding protein inhibition reduced cadmium toxicity, suggesting that CRE-binding protein activation is involved in the cadmium-induced inhibition of claudin-5 and ZO-1 expression and endothelial detachment. These findings provide new insights into the toxicological mechanisms of cadmium-induced endothelial injury and risk of cardiovascular disease.
引用
收藏
页数:13
相关论文
共 31 条
[1]   Arsenite Induces Endothelial Cell Permeability Increase through a Reactive Oxygen Species-Vascular Endothelial Growth Factor Pathway [J].
Bao, Lingzhi ;
Shi, Honglian .
CHEMICAL RESEARCH IN TOXICOLOGY, 2010, 23 (11) :1726-1734
[2]   Mechanism of cadmium-induced nephrotoxicity [J].
Bautista, Claudia J. ;
Arango, Nidia ;
Plata, Consuelo ;
Mitre-Aguilar, Irma B. ;
Trujillo, Joyce ;
Ramirez, Victoria .
TOXICOLOGY, 2024, 502
[3]   Effects of Cadmium on ZO-1 Tight Junction Integrity of the Blood Brain Barrier [J].
Branca, Jacopo Junio Valerio ;
Maresca, Mario ;
Morucci, Gabriele ;
Mello, Tommaso ;
Becatti, Matteo ;
Pazzagli, Luigia ;
Colzi, Ilaria ;
Gonnelli, Cristina ;
Carrino, Donatello ;
Paternostro, Ferdinando ;
Nicoletti, Claudio ;
Ghelardini, Carla ;
Gulisano, Massimo ;
Di Cesare Mannelli, Lorenzo ;
Pacini, Alessandra .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (23)
[4]   Tight junction disruption by cadmium in an in vitro human airway tissue model [J].
Cao, Xuefei ;
Lin, Haixia ;
Muskhelishvili, Levan ;
Latendresse, John ;
Richter, Patricia ;
Heflich, Robert H. .
RESPIRATORY RESEARCH, 2015, 16
[5]   Celastrol prevents cadmium-induced neuronal cell death via targeting JNK and PTEN-Akt/mTOR network [J].
Chen, Sujuan ;
Gu, Chenjian ;
Xu, Chong ;
Zhang, Jinfei ;
Xu, Yijiao ;
Ren, Qian ;
Guo, Min ;
Huang, Shile ;
Chen, Long .
JOURNAL OF NEUROCHEMISTRY, 2014, 128 (02) :256-266
[6]  
Fujie T, 2024, J TOXICOL SCI, V49, P349, DOI 10.2131/jts.49.349
[7]   CREB Is a Novel Nuclear Target of PTEN Phosphatase [J].
Gu, Tingting ;
Zhang, Zhong ;
Wang, Jianli ;
Guo, Junyi ;
Shen, Wen Hong ;
Yin, Yuxin .
CANCER RESEARCH, 2011, 71 (08) :2821-2825
[8]  
Hara T, 2023, J TOXICOL SCI, V48, P655, DOI [10.2131/jts.48.655, 10.2131/jts.48.655]
[9]  
Hara T, 2023, J TOXICOL SCI, V48, P457, DOI 10.2131/jts.48.457
[10]   Biglycan Intensifies ALK5-Smad2/3 Signaling by TGF-1 and Downregulates Syndecan-4 in Cultured Vascular Endothelial Cells [J].
Hara, Takato ;
Yoshida, Eiko ;
Shinkai, Yasuhiro ;
Yamamoto, Chika ;
Fujiwara, Yasuyuki ;
Kumagai, Yoshito ;
Kaji, Toshiyuki .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2017, 118 (05) :1087-1096