Curcumin-primed exosomes mitigate endothelial cell dysfunction during hyperhomocysteinemia

LIFE SCIENCES

卷:107

Article

Kalani, A.¹  Kamat, P. K.¹  Chaturvedi, P.¹  Tyagi, S. C.¹  Tyagi, N.¹ 

[1] Univ Louisville, Dept Physiol & Biophys, Sch Med, Louisville, KY 40202 USA

关键词: Blood-brain barrier;    Curcumin;    Endothelial cells;    Exosomes;    Homocysteine;    Oxidative stress;    Permeability;    Tight junctions;   

DOI  :  10.1016/j.lfs.2014.04.018

来源: Elsevier

【 摘 要 】

Aim: Exosomes, the nano-units (<200 nm), released from diverse cell types in the extracellular body fluid, possess non-immunogenic property and ability to cross the blood-brain barrier (BBB). Since exosomes carry biological information from their cells of origin, we hypothesize that priming cells with potential therapeutic agents release improved cellular contents through exosomes. Curcumin possesses anti-oxidative and anti-inflammatory properties and provides a promising treatment for cerebral diseases and therefore, the aim of the study is to establish that mouse brain endothelial cells (MBECs) when primed with curcumin (7.5 mu M), release an alleviated exosome population that can help recover the endothelial cell (EC) layer permeability. Main methods: Homocysteine is a well-known causative factor of BBB disruption; therefore, homocysteine-treated ECs were used as a model of BBB disruption and curcumin-primed exosomes were utilized to check their potential for mitigating EC disruption. MBECs were treated with curcumin and exosomes were isolated by using ultracentrifugation and immunoprecipitation. Expression levels of junction proteins were detected by Western blot and immunocytochemistry assays. Endothelial cell permeability was analyzed with Fluorescein isothiocyanate-Bovine serum albumin (FITC-BSA) leakage assay using transwell permeable supports. Key findings: Exosomes derived from curcumin-treated (primed) cells (CUR-EXO) alleviated oxidative stress, tight junctions (ZO-1, claudin-5, occludin), adherent junction (VE-cadherin) proteins and EC layer permeability induced during EC damage due to high homocysteine levels (hyperhomocysteinemia). Significance: In conclusion, the study potentiates the use of CUR-EXO for cerebral diseases where drug delivery is still a challenge. The results also pave the way to novel translational therapies for cerebral diseases by maintaining and establishing therapeutic conservatories via primed exosomes. (C) 2014 Elsevier Inc. All rights reserved.

【 授权许可】

Free