Peng J.,National University of Singapore |
Peng J.,Academy of Integrative Medicine |
Yuan Q.,National University of Singapore |
Lin B.,National University of Singapore |
And 8 more authors.
European Journal of Immunology | Year: 2010
SARM (sterile α- and armadillo-motif-containing protein), the fifth identified TIR (Toll-interleukin 1 receptor (IL-1R)) domain-containing adaptors in humans, downregulates NF-κB and IRF3 (interferon-regulatory factor 3)-mediated TLR3 and TLR4 signaling. SARM was characterized as a negative regulator of the TRIF (TIR-domain-containing adaptor protein inducing IFN-β)-dependent pathway via its interaction with TRIF. However, the precise mechanism of action of SARM remains unclear. Here, we demonstrate that SARM inhibits MAPK activation in human embryonic kidney 293 cells, and U937 cells. Both the TRIF- and MyD88-mediated, as well as basal MAPK activity, were repressed, indicating that SARM-mediated inhibition may not be exclusively directed at TRIF or MyD88, but that SARM may also directly inhibit MAPK phosphorylation. The MAPK inhibition effect was verified by RNAi, which increased the basal level of AP-1. Furthermore, LPS challenge upregulated SARM at both the mRNA and protein levels. Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N-terminal and sterile alpha motif domains in the autoregulation of SARM activity. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
PubMed | Fujian University of Traditional Chinese Medicine and Academy of Integrative Medicine
Type: | Journal: Journal of ethnopharmacology | Year: 2015
Gualou Guizhi decoction (GLGZD) prescribed in traditional Chinese medicine has been reported to have protective effects on ischemic stroke. The present study is to investigate the therapeutic effect of GLGZD on ischemic stroke and explore its mode of action.GLGZD was studied on transient middle cerebral artery occlusion (MCAO) followed by reperfusion in vivo, as well as on hippocampal primary neuron cultures in vitro.In vivo, it was shown that GLGZD treatment for 7 days could ameliorate transient middle cerebral artery occlusion (MCAO)-induced neurological deficit, histopathology changes and decrease infarct area. Further study demonstrated that GLGZD inhibited over-activation of astrocytes and apoptosis of neurons and GLGZD promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, the in vitro study revealed that GLGZD treatment protected against NMDA-induced cell apoptosis and neuronal loss, and promoted up-regulation of neuronal specific marker NeuN.Taken together, the present study demonstrates that GLGZD produces a protection in the MCAO model rats via inhibiting over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN and MAP-2. Our study reveals that GLGZD might be a potential neuroprotective agent for stroke and can provide basic data for clinical use.
Lin R.,Academy of Integrative Medicine |
Lin R.,Fujian University of Traditional Chinese Medicine |
Li Z.,Academy of Integrative Medicine |
Li Z.,Fujian University of Traditional Chinese Medicine |
And 9 more authors.
Oncology Letters | Year: 2015
Tulipa edulis Bak (TEB) is an active ingredient in various traditional Chinese medicine compounds and is commonly used to treat swelling and redness, remove toxicity and eliminate stagnation, as well as to prevent and treat certain cancer types. However, the underlying molecular mechanism of the anticancer activity of TEB remains unclear. The aim of the current study was to investigate the effect and underlying mechanism of the ethanolic extract of TEB (EETEB) on SGC‑7901 human gastric carcinoma cells. An MTT assay was performed to analyze cell viability. In addition, transmission electron microscopy, an Annexin V/fluorescein isothiocyanate assay, a JC‑1 assay and laser scanning confocal microscopy with DAPI staining were used to determine the rate of apoptosis. Furthermore, reverse transcription‑polymerase chain reaction and western blot analysis were used to detect the expression levels of the apoptosis gene and protein. EETEB was identified to inhibit the growth of SGC‑7901 cells in a dose‑dependent manner and induce changes in cell morphology. At the molecular level, EETEB induced SGC‑7901 cell DNA fragmentation, loss of plasma membrane and asymmetrical collapse of the mitochondrial membrane potential, while it increased the expression of pro‑apoptotic B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein and reduced expression of anti‑apoptotic Bcl‑2. Thus, the results of the current study revealed that the application of EETEB may inhibit the growth of the SGC‑7901 cells due to mitochondria‑mediated apoptosis. © 2015 Spandidos Publications. All rights reserved.
Ko J.-K.,Robert Wood Johnson Medical School |
Choi K.-H.,Robert Wood Johnson Medical School |
Peng J.,The University of Oklahoma Health Sciences Center |
Peng J.,Academy of Integrative Medicine |
And 5 more authors.
Journal of Biological Chemistry | Year: 2011
Bcl-2 homology domain-3 (BH3) peptides are potent cancer therapeutic reagents that target regulators of apoptotic cell death in cancer cells. However, their cytotoxic effects are affected by different expression levels of Bcl-2 family proteins. We recently found that the amphipathic tail-anchoring peptide (ATAP) from Bfl-1, a bifunctional Bcl-2 family member, produced strong pro-apoptotic activity by permeabilizing the mitochondrial outer membrane. Here, we test whether the activity of ATAP requires other cellular factors and whether ATAP has an advantage over the BH3 peptides in targeting cancer cells. Confocal microscopic imaging illustrates specific targeting of ATAP to mitochondria, whereas BH3 peptides show diffuse patterns of cytosolic distribution. Although the pro-apoptotic activities of BH3 peptides are largely inhibited by either overexpression of anti-apoptotic Bcl-2 or Bcl-xL or nullification of pro-apoptotic Bax and Bak in cells, the pro-apoptotic function of ATAP is not affected by these cellular factors. Reconstitution of synthetic ATAP into liposomal membranes results in release of fluorescent molecules of the size of cytochrome c from the liposomes, suggesting that the membrane permeabilizing activity of ATAP does not require additional protein factors. Because ATAP can target to the mitochondrial membrane and its pro-apoptotic activity does not depend on the content of Bcl-2 family proteins, it represents a promising candidate for anti-cancer drugs that can potentially overcome the intrinsic apoptosis-resistant nature of cancer cells. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.