Mytilec, a mussel R-type lectin, interacts with surface glycan GB3 on burkitt's lymphoma cells to trigger apoptosis through multiple pathways

Imtiaj Hasan, Shigeki Sugawara, Yuki Fujii, Yasuhiro Koide, Daiki Terada, Naoya Iimura, Toshiyuki Fujiwara, Keisuke G. Takahashi, Nobuhiko Kojima, Sultana Rajia, Sarkar M.A. Kawsar, Robert A. Kanaly, Hideho Uchiyama, Masahiro Hosono, Yukiko Ogawa, Hideaki Fujita, Jiharu Hamako, Taei Matsui, Yasuhiro Ozeki

研究成果: Article

25 引用 (Scopus)

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MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis); shows strong binding affinity to globotriose (Gb3: Galα1-4Galβ1-4Glc). MytiLec revealed β-trefoil folding as also found in the ricin B-subunit type (R-type) lectin family, although the amino acid sequences were quite different. Classification of R-type lectin family members therefore needs to be based on conformation as well as on primary structure. MytiLec specifically killed Burkitt's lymphoma Ramos cells, which express Gb3. Fluorescein-labeling assay revealed that MytiLec was incorporated inside the cells. MytiLec treatment of Ramos cells resulted in activation of both classical MAPK/extracellular signal-regulated kinase and extracellular signal-regulated kinase (MEK-ERK) and stress-activated (p38 kinase and JNK) Mitogen-activated protein kinases (MAPK) pathways. In the cells, MytiLec treatment triggered expression of tumor necrosis factor (TNF)-α (a ligand of death receptor-dependent apoptosis) and activation of mitochondria-controlling caspase-9 (initiator caspase) and caspase-3 (activator caspase). Experiments using the specific MEK inhibitor U0126 showed that MytiLec-induced phosphorylation of the MEK-ERK pathway up-regulated expression of the cyclin-dependent kinase inhibitor p21, leading to cell cycle arrest and TNF-α production. Activation of caspase-3 by MytiLec appeared to be regulated by multiple different pathways. Our findings, taken together, indicate that the novel R-type lectin MytiLec initiates programmed cell death of Burkitt's lymphoma cells through multiple pathways (MAPK cascade, death receptor signaling; caspase activation) based on interaction of the lectin with Gb3-containing glycosphingolipid-enriched microdomains on the cell surface.

元の言語English
ページ(範囲)7377-7389
ページ数13
ジャーナルMarine Drugs
13
発行部数12
DOI
出版物ステータスPublished - 01-12-2015

All Science Journal Classification (ASJC) codes

  • Drug Discovery

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    Hasan, I., Sugawara, S., Fujii, Y., Koide, Y., Terada, D., Iimura, N., Fujiwara, T., Takahashi, K. G., Kojima, N., Rajia, S., Kawsar, S. M. A., Kanaly, R. A., Uchiyama, H., Hosono, M., Ogawa, Y., Fujita, H., Hamako, J., Matsui, T., & Ozeki, Y. (2015). Mytilec, a mussel R-type lectin, interacts with surface glycan GB3 on burkitt's lymphoma cells to trigger apoptosis through multiple pathways. Marine Drugs, 13(12), 7377-7389. https://doi.org/10.3390/md13127071