MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt’s Lymphoma Cells to Trigger Apoptosis through Multiple Pathways

Marine Drugs

Imtiaj Hasan¹  Shigeki Sugawara⁵  Yuki Fujii²  Yasuhiro Koide¹  Daiki Terada³  Naoya Iimura¹  Toshiyuki Fujiwara²  Keisuke G. Takahashi⁶  Nobuhiko Kojima¹  Sultana Rajia¹  Sarkar M. A. Kawsar¹  Robert A. Kanaly¹  Hideho Uchiyama¹  Masahiro Hosono⁵  Yukiko Ogawa²  Hideaki Fujita²  Jiharu Hamako⁴  Taei Matsui⁴  Yasuhiro Ozeki¹ 

[1] Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027, Japan;Department of Pharmacy, Faculty of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan;Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan;Department of Biology, School of Health Sciences, Fujita Health University, Toyoake, Aichi 470-1192, Japan;Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan;Graduate School of Agricultural Science, Tohoku University, 1-1 Amamiya-machi, Tsutsumidori, Aoba-ku, Sendai 230-0045, Japan;

关键词: Burkitt’s lymphoma cells;    caspase-9/3;    globotriose (Gb3);    JNK;    Mytilus galloprovincialis;    MEK/ERK;    MytiLec;    p21: p38 kinase;    R-type lectin;    TNF-α;    β-trefoil;   

DOI  :  10.3390/md13127071

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.