Concanavalin A induces autophagy in hepatoma cells and has a therapeutic effect in a murine in situ hepatoma model

Chang, Chih Peng; Yang, Ming; Liu, Hsiao Sheng; Lin, Yee Shin; Lei, Huan Yao

doi:10.1002/hep.21509

Cited by 162 publications

(138 citation statements)

References 26 publications

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“…In addition, ConA has been reported to show anti-tumor effects, which are mediated by the intrahepatic activation of both NK cells (Miyagi et al 2004) and CD8 + T cells (Chang et al 2007;Lei and Chang 2009). ConA is also known to induce anti-fungal response (Felipe et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Ando

Yasuoka

Mishima

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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T cell activation is regulated by two distinct signals, signal one and two. Concanavalin A (ConA) is an antigen-independent mitogen and functions as signal one inducer, leading T cells to polyclonal proliferation. CD28 is known to be one of major costimulatory receptors and to provide signal two in the ConA-induced T cell proliferation. Here, we have studied the implication of other costimulatory pathways in the ConA-mediated T cell proliferation by using soluble recombinant proteins consisting of an extracellular domain of costimulatory receptors and Fc portion of human IgG. We found that T cell proliferation induced by ConA, but not PMA plus ionomycin or anti-CD3 mAb, is significantly inhibited by HVEM-Ig, even in the presence of CD28 signaling. Moreover, the high concentration of HVEM-Ig molecules almost completely suppressed ConA-mediated T cell proliferation. These results suggest that HVEM might play more important roles than CD28 in ConA-mediated T cell proliferation.

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Section: Discussionmentioning

confidence: 99%

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Ando

Yasuoka

Mishima

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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“…It is therefore possible to suppress autophagy in order to enhance the efficacy of these agents. This idea has been tested successfully in tumor cells originated from the liver 112 or other organs. 62,[113][114][115] This approach could be particularly useful for cancer cells resistant to standard treatment as a result of a weakened apoptosis response because disabling autophagy could lead to enhanced death stimulation and/or activation of additional death mechanisms, such as necrosis.…”

Section: Autophagy and Cell Death Implications In Tissue Injury Tummentioning

confidence: 99%

Autophagy in the liver

2008

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A great part of our current understanding of mammalian macroautophagy is derived from studies of the liver. The term "autophagy" was introduced by Christian de Duve in part based on ultrastructural changes in rat liver following glucagon injection. Subsequent morphological, biochemical, and kinetics studies of autophagy in the liver defined the basic process of autophagosome formation, maturation, and degradation and the regulation of autophagy by hormones, phosphoinositide 3-kinases, and mammalian target of rapamycin. It is now clear that macroautophagy in the liver is important for the balance of energy and nutrients for basic cell functions, the removal of misfolded proteins resulting from genetic mutations or pathophysiological stimulations, and the turnover of major subcellular organelles such as mitochondria, endoplasmic reticulum, and peroxisomes under both normal and pathophysiological conditions. Disturbance of autophagy function in the liver could thus have a major impact on liver physiology and liver disease. (HEPATOLOGY 2008;47: 1773-1785.)

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“…34 Conversely, BNIP3 expression was induced early before the conversion of LC3-1 to LC3-II, and knockdown of BNIP3 could prevent LC3 conversion and autophagic cell death. 35 BNIP3 is also induced by arsenic trioxide, 12 ceramide 16 or concanavalin A, 35 and concurrent induction of autophagy and cell death is mediated by BNIP3 in response to these stimuli. Loss of Rb has also been found to induce BNIP3-dependent autophagic cell death.…”

Section: Bnip3mentioning

confidence: 99%

The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death

2009

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Bcl-2 nineteen-kilodalton interacting protein (BNIP3) is a BH-3-only Bcl-2 family member whose expression levels increase during stress such as hypoxia through hypoxia-inducing factor-1-dependent or -independent mechanisms. When BNIP3 expression is induced, it localizes to the mitochondria and triggers a loss of membrane potential, and an increase in the reactive oxygen species production, which often leads to cell death. Cells under normal growth conditions suppress BNIP3 expression through transcriptional repression. There is considerable debate in the literature regarding what type of cell death is induced by BNIP3. It has been observed that BNIP3 could induce necrosis, autophagy and/or apoptosis. In contrast, other studies indicate that BNIP3 could promote cell survival. Besides its cell death regulation, BNIP3 plays a key role in the pathogenicity of many diseases. In cardiac infarction, loss of BNIP3 expression has been shown to reduce the number of damaged cardiomyocytes after ischemia and reperfusion. BNIP3 expression also plays an important role in the deregulation of cell death in many cancers. In this review, we will discuss the different and often contradictory mechanisms of BNIP3 regulation of cell death and the role that BNIP3 may play in diseases. Bcl-2 nineteen-kilodalton interacting protein (BNIP3) belongs to the Bcl-2 homology domain (BH3)-only Bcl-2 family members because it only contains a putative BH3 domain. 1 The other major domains found in BNIP3 are the PEST domain that targets BNIP3 for degradation, a conserved domain that is conserved from Caenorhabditis elegans to humans and a transmembrane (TM) domain, which targets BNIP3 to the mitochondria (Figure 1). 2 BH3-only containing proteins act as rheostats regulating apoptosis through their BH3 domain by binding to antiapoptotic Bcl-2 family members. However, BNIP3 differs from these members, as its BH3 domain fails to interact with antiapoptotic Bcl-2 family members. 3 Furthermore, deletions of the BH3 domain fail to affect the ability of BNIP3 to induce cell death. 4 Unlike other BH3-only family members, BNIP3 interacts with Bcl-2 and Bcl-X L through its TM domain and N terminus (amino acids 1-49). 3 Deletion of the TM domain blocks the ability of BNIP3 to induce cell death. 4 BNIP3 migrates at 30 and 60 kDa, indicating that BNIP3 is a protein that forms homodimers. This homodimerization is primarily through the TM domain of BNIP3. The unique structure of the TM domain suggests that BNIP3 dimers could act as proton channels in the outer mitochondrial membrane increasing ion conductance. 5 Serine 172 and histidine (His) 173 are residues that are present in the dimerization interface of BNIP3. These residues interact by hydrogen bonds and are essential for dimer formation. 6 Furthermore, mutation of the His 173 to alanine completely abrogated the ability of BNIP3 to induce cell death. 7 Bcl-2 and Bcl-X L can compete for binding to the TM domain, which blocks BNIP3 homodimerization and abrogates the ability of BNIP3 to induce cell death (Fi...

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Concanavalin A induces autophagy in hepatoma cells and has a therapeutic effect in a murine in situ hepatoma model

Cited by 162 publications

References 26 publications

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Concanavalin A-mediated T cell proliferation is regulated by herpes virus entry mediator costimulatory molecule

Autophagy in the liver

The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death

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