Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1
Abstract
Previous studies revealed that carboxyl-terminal fragment containing the globular domain of adiponectin exists in human plasma. Although it is proposed that the globular fragment is generated by proteolytic cleavage, the place and responsible enzyme of the cleavage are still unclear. In this study, we evaluated the activity to cleave adiponectin in culture medium of several cell lines in vitro. Adiponectin cleavage into several carboxyl-terminal fragments containing the globular domain was observed in the medium of phorbol 12-myristate 13-acetate-stimulated monocytic cell lines THP-1 and U937. The molecular masses of the major products were 25, 20, and 18 kDa. The cleavage was thought to be mediated by leukocyte elastase (also known as neutrophil elastase) based on the following observations. First, the cleavage was inhibited by serine-protease inhibitors [phenylmethylsulfonylfluoride, Pefabloc SC (Roche Diagnostics, Basel, Switzerland) and aprotinin] and by the leukocyte elastase-specific peptide inhibitor MeOSuc-AAPV-CMK. Second, no activity was detected after THP-1 cells had fully differentiated into macrophages. Third, purified leukocyte elastase cleaved adiponectin with the same cleavage pattern as THP-1 cells. Finally, leukocyte elastase secreted by activated neutrophils cleaved adiponectin into the globular fragments. Amino-terminal sequence analysis revealed that cleavage sites of adiponectin by purified leukocyte elastase were between 38Thr and 39Cys, 40Ala and 41Gly, 44Ala and 45Gly, 91Ala and 92Glu, and 110Ala and 111Ala (the numbering of the positions of the amino acids starts at the signal sequence), suggesting that the cleavage occurs in the collagenous domain. These data indicate that the cleavage of adiponectin by leukocyte elastase secreted from activated monocytes and/or neutrophils could be a candidate for the mechanism of the generation of the globular fragment of adiponectin.
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After injury, immune cells, including M1 macrophages, are recruited to the lesion site where they produce and release elastases that cleave native ApN into its globular ApN form (gApN).
“After injury, immune cells, including M1 macrophages, are recruited to the lesion site where they produce and release elastases that cleave native ApN into its globular ApN form (gApN) [8].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [8]
Cites
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Self-citationParadoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J.-I., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0255 · Cited by 4,856 · see citing works
Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238 · see citing works
Self-citationA Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes
Scherer, P. E., Williams, S. P., Fogliano, M., Baldini, G., & Lodish, H. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.26746 · Cited by 3,238 · see citing works
Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
Yamauchi, T., Kamon, J., Ito, Y., Tsuchida, A., Yokomizo, T., Kita, S., Sugiyama, T., Miyagishi, M., Hara, K., Tsunoda, M., et al. (2003) · Nature · doi:10.1038/nature01705 · Cited by 3,176 · see citing works
Plasma Concentrations of a Novel, Adipose-Specific Protein, Adiponectin, in Type 2 Diabetic Patients
Hotta, K., Funahashi, T., Arita, Y., Takahashi, M., Matsuda, M., Okamoto, Y., Iwahashi, H., Kuriyama, H., Ouchi, N., Maeda, K., et al. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.6.1595 · Cited by 3,133 · see citing works
The adipocyte-secreted protein Acrp30 enhances hepatic insulin action
Berg, A. H., Combs, T. P., Du, X., Brownlee, M., & Scherer, P. E. (2001) · Nature Medicine · doi:10.1038/90992 · Cited by 2,526 · see citing works
AdipoQ Is a Novel Adipose-specific Gene Dysregulated in Obesity
Hu, E., Liang, P., & Spiegelman, B. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.18.10697 · Cited by 2,239 · see citing works
Diet-induced insulin resistance in mice lacking adiponectin/ACRP30
Maeda, N., Shimomura, I., Kishida, K., Nishizawa, H., Matsuda, M., Nagaretani, H., Furuyama, N., Kondo, H., Takahashi, M., Arita, Y., et al. (2002) · Nature Medicine · doi:10.1038/nm724 · Cited by 2,086 · see citing works
Maeda, K., Okubo, K., Shimomura, I., Funahashi, T., Matsuzawa, Y., & Matsubara, K. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0587 · Cited by 2,081 · see citing works
Fruebis, J., Tsao, T., Javorschi, S., Ebbets-Reed, D., Erickson, M., Yen, F. T., Bihain, B. E., & Lodish, H. F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.2005 · Cited by 1,987 · see citing works
Ouchi, N., Kihara, S., Arita, Y., Okamoto, Y., Maeda, K., Kuriyama, H., Hotta, K., Nishida, M., Takahashi, M., Muraguchi, M., et al. (2000) · Circulation · doi:10.1161/01.cir.102.11.1296 · Cited by 1,730 · see citing works
Yokota, T., Oritani, K., Takahashi, I., Ishikawa, J., Matsuyama, A., Ouchi, N., Kihara, S., Funahashi, T., Tenner, A. J., Tomiyama, Y., et al. (2000) · Blood · doi:10.1182/blood.v96.5.1723 · Cited by 1,294 · see citing works
Ouchi, N., Kihara, S., Arita, Y., Nishida, M., Matsuyama, A., Okamoto, Y., Ishigami, M., Kuriyama, H., Kishida, K., Nishizawa, H., et al. (2001) · Circulation · doi:10.1161/01.cir.103.8.1057 · Cited by 1,275 · see citing works
Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation
Kubota, N., Terauchi, Y., Yamauchi, T., Kubota, T., Moroi, M., Matsui, J., Eto, K., Yamashita, T., Kamon, J., Satoh, H., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200251200 · Cited by 1,213 · see citing works
Self-citationDisruption of adiponectin causes insulin resistance and neointimal formation
Froguel, P. (2002) · HAL · Cited by 1,126 · see citing works
Structure-Function Studies of the Adipocyte-secreted Hormone Acrp30/Adiponectin
Pajvani, U. B., Du, X., Combs, T. P., Berg, A. H., Rajala, M. W., Schulthess, T., Engel, J., Brownlee, M., & Scherer, P. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m207198200 · Cited by 1,090 · see citing works
Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice
Okamoto, Y., Kihara, S., Ouchi, N., Nishida, M., Arita, Y., Kumada, M., Ohashi, K., Sakai, N., Shimomura, I., Kobayashi, H., et al. (2002) · Circulation · doi:10.1161/01.cir.0000042707.50032.19 · Cited by 1,030 · see citing works
Impaired Multimerization of Human Adiponectin Mutants Associated with Diabetes
Waki, H., Yamauchi, T., Kamon, J., Ito, Y., Uchida, S., Kita, S., Hara, K., Hada, Y., Vasseur, F., Froguel, P., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300365200 · Cited by 981 · see citing works
Self-citationIsolation and Characterization of GBP28, a Novel Gelatin-Binding Protein Purified from Human Plasma
Nakano, Y., Tobe, T., Choi-Miura, N.-H., Mazda, T., & Tomita, M. (1996) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021483 · Cited by 915 · see citing works
Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis
Yamauchi, T., Kamon, J., Waki, H., Imai, Y., Shimozawa, N., Hioki, K., Uchida, S., Ito, Y., Takakuwa, K., Matsui, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209033200 · Cited by 911 · see citing works
Self-citationRole of Adiponectin in Preventing Vascular Stenosis
Matsuda, M., Shimomura, I., Sata, M., Arita, Y., Nishida, M., Maeda, N., Kumada, M., Okamoto, Y., Nagaretani, H., Nishizawa, H., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206083200 · Cited by 809 · see citing works
An Adipocyte-Derived Plasma Protein, Adiponectin, Adheres to Injured Vascular Walls
Okamoto, Y., Arita, Y., Nishida, M., Muraguchi, M., Ouchi, N., Takahashi, M., Igura, T., Inui, Y., Kihara, S., Nakamura, T., et al. (2000) · Hormone and Metabolic Research · doi:10.1055/s-2007-978586 · Cited by 567 · see citing works
Tkalcevic, J., Novelli, M. R., Phylactides, M., Iredale, J. P., Segal, A. W., & Roes, J. (2000) · Immunity · doi:10.1016/s1074-7613(00)80173-9 · Cited by 379 · see citing works
Degradation of Outer Membrane Protein A in <i>Escherichia coli</i> Killing by Neutrophil Elastase
Belaaouaj, A. A., Kim, K. S., & Shapiro, S. D. (2000) · Science · doi:10.1126/science.289.5482.1185 · Cited by 363 · see citing works
Adkison, A. M., Raptis, S. Z., Kelley, D. G., & Pham, C. T. N. (2002) · Journal of Clinical Investigation · doi:10.1172/jci13462 · Cited by 362 · see citing works
Adkison, A. M., Raptis, S. Z., Kelley, D. G., & Pham, C. T. N. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0213462 · Cited by 359 · see citing works
Tsao, T., Murrey, H. E., Hug, C., Lee, D. H., & Lodish, H. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200312200 · Cited by 352 · see citing works
Neutrophil Elastase in Human Atherosclerotic Plaques
DOLLERY, C. M., Owen, C. A., Sukhova, G. K., et al. (2003) · Circulation · doi:10.1161/01.cir.0000072792.65250.4a · Cited by 226 · see citing works
Campbell, E. J., Silverman, E. K., & Campbell, M. A. (1989) · The Journal of Immunology · doi:10.4049/jimmunol.143.9.2961 · Cited by 183 · see citing works
Campbell, E. J., Cury, J., Shapiro, S. D., et al. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.4.1286 · Cited by 177 · see citing works
Yokota, T., Meka, C. S. R., Medina, K. L., Igarashi, H., Comp, P. C., Takahashi, M., Nishida, M., Oritani, K., Miyagawa, J.-I., Funahashi, T., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14506 · Cited by 141 · see citing works
Change in Expression of GBP28/Adiponectin in Carbon Tetrachloride-Administrated Mouse Liver
Yoda-Murakami, M., Taniguchi, M., Takahashi, K., Kawamata, S., Saito, K., Choi-Miura, N.-H., & Tomita, M. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5134 · Cited by 126 · see citing works
Yokota, T., Meka, C. S. R., Medina, K. L., Igarashi, H., Comp, P. C., Takahashi, M., Nishida, M., Oritani, K., Miyagawa, J., Funahashi, T., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214506 · Cited by 125 · see citing works
Åbrink, M., Gobl, A., Huang, R., et al. (1994) · PubMed · Cited by 99 · see citing works
Ishikawa, Y., Akasaka, Y., Ishii, T., Yoda-Murakami, M., Choi-Miura, N.-H., Tomita, M., Ito, K., Zhang, L., Akishima, Y., Ishihara, M., et al. (2002) · Histopathology · doi:10.1046/j.1365-2559.2003.01518.x · Cited by 50 · see citing works
Welgus, H. G., Senior, R. M., Parks, W. C., Kahn, A. J., Ley, T. J., Shapiro, S. D., & Campbell, E. J. (1992) · PubMed · Cited by 36 · see citing works
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Awazawa, M., Ueki, K., Inabe, K., Yamauchi, T., Kubota, N., Kaneko, K., Kobayashi, M., Iwane, A., Sasako, T., Okazaki, Y., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.02.010 · Cited by 277 · see citing works
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Zhou, L., Deepa, S. S., Etzler, J. C., Ryu, J., Mao, X., Fang, Q., Liu, D. D., Torres, J. M., Jia, W., Lechleiter, J. D., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.028357 · Cited by 212 · see citing works
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- Authors
- Waki, H., Yamauchi, T., Kamon, J., Kita, S., Ito, Y., Hada, Y., Uchida, S., Tsuchida, A., Takekawa, S., & Kadowaki, T.
- Affiliations
- Japan Science and Technology Agency (JP)
- The University of Tokyo (JP)
- Corresponding author
- Kadowaki, Takashi
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-02-01
- Volume
- 146
- Issue
- 2
- Pages
- 790-796
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2134614230
- Cited by
- 319
- References
- 37
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 12 · 2019: 19 · 2018: 14 · 2017: 15 · 2016: 6 · 2015: 18 · 2014: 19 · 2013: 26 · 2012: 28
- FWCI
- 11.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- adiponectin, leukocyte elastase, neutrophil elastase, proteolytic cleavage, THP-1 cells, U937 cells, neutrophils, collagenous domain, cleavage site, serine protease inhibitors
- MeSH terms
- Amino Acid Sequence, Cell Differentiation, Humans, Macrophages, Molecular Sequence Data, Monocytes, Serine Endopeptidases, Protein Structure, Tertiary, Leukocyte Elastase, U937 Cells, Sequence Analysis, Protein, Intercellular Signaling Peptides and Proteins, Adiponectin
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