Effect of Heat Shock Treatment on Endothelial Cell Integrity after Histamine Challenge

Translated Titles





王士忠(Shih-Chung Wang);楊瑞成(Rei-Cheng Yang);張明裕(Ming-Yuh Chang);呂宗禧(Tsong-Shi Lu);曹龍彥(Long-Yen Tsao)

Key Words

細胞骨架蛋白 ; 熱休克蛋白 ; 組織胺 ; 人類臍靜脈內皮細胞 ; 細胞緊密連接蛋白 ; F-actin ; heat shock protein ; histamine ; HUVEC ; ZO-1, occludin


The Changhua Journal of Medicine

Volume or Term/Year and Month of Publication

14卷1期(2016 / 03 / 01)

Page #

1 - 11

Content Language


Chinese Abstract

內皮細胞及其完整性在維持循環恆定上占有主要的角色。我們之前的研究顯示熱休克處置可以減少過敏性休克所引起的蛋白質流失與低血壓。此外,在血腦障壁受高滲透壓影響而打開時,熱休克處置可以維持腦血管的通透性。在本研究中,我們藉由組織胺刺激人類臍靜脈內皮細胞,造成其通透性改變,探討熱休克蛋白72 ( 熱休克後的主要蛋白) 在維持內皮細胞完整性上的可能機轉。藉由免疫細胞化學染色顯示,未經熱休克處理的經組織胺刺激人類臍靜脈內皮細胞,其細胞緊密連接蛋白(ZO-1及occludin) 明顯減少,且其程度與細胞骨架蛋白(F-actin) 的減少成比例。在組織胺刺激人類臍靜脈內皮細胞前,經由熱休克處理可以防止此一現象。經由熱休克處理的內皮細胞,表現大量的熱休克蛋白72。我們同時也顯示出熱休克蛋白72 與細胞緊密連接蛋白(ZO-1 及occludin) 同時表現在經由熱休克處理的內皮細胞。總結來說,經組織胺刺激人類臍靜脈內皮細胞所引起的細胞通透性的變化,可以經由事先的熱休克處理而減緩,其機轉可能藉由熱休克蛋白72 對細胞緊密連接蛋白(ZO-1 及occludin)與細胞骨架蛋白(F-actin) 的保存。

English Abstract

Endothelial cells and endothelial cell integrity play a central role in circulatory homeostasis. Our previous study indicated that heat shock treatment reduces protein leakage and attenuates the hypotension caused by anaphylactic shock. Also, heat shock treatment maintains cerebral vascular permeability, while the blood brain barrier is opened by high osmotic stress. In this study we investigated the potential mechanism by which heat shock protein 72 (Hsp72), the major product after heat shock, maintains cellular integrity of cultured histamine-induced human umbilical vein endothelial cells (HUVECs) upon challenge by histamine. Tight junction proteins (ZO-1 and occludin) and a cytoskeleton component (F-actin) were evaluated by an immunocytochemical study. The immunochemical density of ZO-1 and occludin was clearly decreased in the non-heated cells after histamine challenge, and associated with the proportional decline of F-actin. The adverse phenomenon was prevented in the heated cells in which Hsp72 was significantly over-expressed. It was further demonstrated that Hsp72 could be exclusively coimmunoprecipitated with ZO-1 or occludin in heated cells. In conclusion, histamine-induced conformational alteration of HUVECs is attenuated by previous heat shock treatment, and the Hsp72-mediated preservation of tight junction proteins, as well as cytoskeletal structure, could be the possible mechanism of action.

Topic Category 醫藥衛生 > 醫藥衛生綜合