期刊
CELLS
卷 9, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/cells9030631
关键词
apoptosis; curcumin nanosphere; gastrointestinal cell death; Vibrio vulnificus; VvhA
类别
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2017R1A2B2007741, 2019R1A2C1088927]
- National Research Foundation of Korea [2019R1A2C1088927, 2017R1A2B2007741] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Curcumin, a hydrophobic polyphenol of turmeric, has a variety of biological functions as a herbal supplement, but its poor gastric absorption rate is one of the major factors limiting its oral bioavailability. In the present study, we have investigated the functional role of a nanosphere loaded with curcumin (CN) during host cell death elicited by the Gram-negative bacterium V. vulnificus in human gastrointestinal epithelial HT-29 cells and an ileal-ligated mouse model. The recombinant protein (r) VvhA produced by V. vulnificus significantly reduced the viability of HT-29 cells. The cytotoxic effect of rVvhA was restored upon a treatment with CN (100 ng/mL), which had shown 1000-fold higher anti-apoptotic efficacy than curcumin. CN inhibited the phosphorylation of c-Src and PKC mediated by intracellular ROS responsible for the distinctive activation of the MAPKs in rVvhA-treated HT-29 cells. Interestingly, CN significantly restored the expression of Bax, Bcl-2, and cleaved caspase-3 as regulated by the phosphorylation of NF-kappa B. In mouse models of V. vulnificus infection, treatment with CN had a blocking effect that elevated the levels of TUNEL-positive DNA fragmentation and apoptosis-related proteins. These results indicate that CN is a functional agent that manipulates the V. vulnificus VvhA signaling pathway responsible for gastrointestinal cell death.
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