HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Mitochondria-dependent apoptosis of activated T lymphocytes induced by astin C, a plant cyclopeptide, for preventing murine experimental colitis.

Abstract
Facilitating T-cell apoptosis is implicated as an effective therapeutic strategy for treatment of T cell-mediated disease, including inflammatory bowel disease. Here, we report that astin C, a plant cyclopeptide isolated from the roots of Aster tataricus (Compositae), induced apoptosis of activated T cells in a mitochondria-dependent but Fas-independent manner in that such activity was still observed in T cells from Fas-mutated MRLlpr/lpr mice. Although caspase 8 was not activated, astin C treatment led to the cleavage of caspase 9 and caspase 3, the upregulation of Bad protein expression as well as release of cytochrome c in activated T cells. Astin C did not induce the expression of GRP78 and GADD153, excluding involvement of endoplasmic reticulum stress-mediated pathway. Moreover, oral administration of astin C protected mice against TNBS-induced colonic inflammation, as assessed by a reduced colonic weight/length ratio and histological scoring. Administering astin C significantly decreased serum levels of TNF-α, IL-4 and IL-17, accompanied with the induction of apoptosis in activated T cells in vivo. The results demonstrate, for the first time, the ability of astin C to induce apoptosis in activated T cells and its potential use in the treatment of colonic inflammation.
AuthorsYan Shen, Qiong Luo, Huimin Xu, Fangyuan Gong, Xiaobin Zhou, Yang Sun, Xuefeng Wu, Wen Liu, Guangzhi Zeng, Ninghua Tan, Qiang Xu
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 82 Issue 3 Pg. 260-8 (Aug 01 2011) ISSN: 1873-2968 [Electronic] England
PMID21569765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Cytokines
  • Endoplasmic Reticulum Chaperone BiP
  • Hspa5 protein, mouse
  • Peptides, Cyclic
  • astin C
  • Trinitrobenzenesulfonic Acid
Topics
  • Animals
  • Anti-Inflammatory Agents (chemistry, pharmacology)
  • Apoptosis (drug effects, physiology)
  • Aster Plant (chemistry)
  • Cells, Cultured
  • Colitis (chemically induced, prevention & control)
  • Cytokines (genetics, metabolism)
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Gene Expression Regulation (drug effects)
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria (metabolism)
  • Peptides, Cyclic (chemistry, pharmacology)
  • Plant Roots (chemistry)
  • T-Lymphocytes (drug effects, physiology)
  • Trinitrobenzenesulfonic Acid (toxicity)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: