2012 Fiscal Year Final Research Report
The cholesterol metabolism of neuroendocrine cells and crosstalk of the hormone secretion
| Project/Area Number |
22570133
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Akita Prefectural University (2011-2012)
Gunma University (2010) |
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Principal Investigator |
HOSAKA Masahiro 秋田県立大学, 生物資源科学部, 教授 (80311603)
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| Co-Investigator(Renkei-kenkyūsha) |
WATANABE Tsuyoshi 旭川医科大学, 医学部, 教授 (80220903)
YAMADA Keiichi 群馬大学, 工学研究科, 助教 (70323334)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ホルモンと生理活性物質 |
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| Research Abstract |
Prior to secretion, regulated peptide hormones are selectively sorted to secretory granules (SGs) at the trans-Golgi network (TGN) in endocrine cells. Secretogranin III (SgIII) appears to facilitate SG sorting process by tethering of protein aggregates containing chromogranin A (CgA) and peptide hormones to the cholesterol-rich SG membrane (SGM). Here, we evaluated the role of SgIII in SG sorting in AtT-20 cells transfected with small interfering RNA targeting SgIII. In the SgIII-knockdown cells, the intracellular retention of CgA was greatly impaired, and only a trace amount of CgA was localized within the vacuoles formed in the TGN, confirming the significance of SgIII in both the tethering of CgA-containing aggregates and the establishment of the proper SG morphology. Although the intracellular retention of proopiomelanocortin (POMC) was considerably impaired in SgIII-knockdown cells, residual ACTH/POMC was still localized to some few remaining SGs together with another granin protein, secretogranin II (SgII), and was secreted in a regulated manner. Biochemical analyses indicated that SgII bound directly to the SGM in a cholesterol-dependent manner and was able to retain the aggregated form of POMC, revealing a latent redundancy in the SG sorting and retention mechanisms, that ensures the regulated secretion of bioactive peptides.
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[Journal Article] Chronic exercise enhances insulin secretion ability of pancreatic islets without change in insulin content in non-diabetic rats2013
Author(s)
Tsuchiya, M., Manabe Y., Yamada, K., Furuichi, Y., Hosaka, M., Fujii, N.
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Journal Title
BBRC
Volume: 430
Pages: 676-682
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[Journal Article] Multiple sorting systems for secretory granules ensure the regulated secretion of peotide hormones2013
Author(s)
Sun, M., Watanabe, T., Bochimoto, H., Sakai, Y., Torii, S., Takeuchi, T., Hosaka, M.
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Journal Title
Traffic
Volume: 14
Pages: 205-218
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[Journal Article] A unique ball-shapeed Golgi apparatus in the rat pituitary ganadotrope: its functional implications in relation to the arrangement of microtuble network2012
Author(s)
Watanabe, T., Sakai, Y., Koga, D., Bochimoto, H., Hira, Y., Hosaka, M., Ushiki, T.
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Journal Title
J. Histochem. Cytochem
Volume: 60
Pages: 588-602
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[Journal Article] Silylation Enhancement of Photodynamic Activity of Tetraphenylporphyrin Derivative2011
Author(s)
Horiuchi, H., Kameya, T., Hosaka, M., Yoshimura, K., Kyushin, S., Matsumoto, H., Okutsu, T., Takeuchi, T., Hiratsuka, H.
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Journal Title
J. Photochem. Photobiol
Volume: 221
Pages: 98-104
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[Journal Article] Cyclophilin C-associated protein regulation of phagocytic functions via NFAT activation in macrophages2011
Author(s)
Yamaguchi, R., Hosaka, M., Torii, S., Hou, N., Saito, N., Yoshimoto, Y., Imai., H., Takeuchi, T.
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Journal Title
Brain Res
Volume: 1397
Pages: 55-65
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[Journal Article] Luminal Interaction of Phogrin with Carboxypeptidase E for Effective Targeting to Secretory Granules2011
Author(s)
Saito, N., Takeuchi, T., Kawano, A., Hosaka, M., Hou, N., Torii, S.
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Journal Title
Traffic
Volume: 12
Pages: 499-506
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[Journal Article] (The first two authors contributed equally to this work.): Cholesterol Biosynthesis Pathway Intermediates and Inhibitors Regulate Glucose-stimulated Insulin Secretion and Secretory Granule Formation in Pancreatic beta-Cells2010
Author(s)
Tsuchiya, M., Hosaka, M., Moriguchi, T., Zhang, S., Suda, M., Yokota-Hashimoto, H., Shinozuka, K., Takeuchi, T
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Journal Title
Endocrinology
Volume: 151
Pages: 4705-4716
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[Journal Article] (The first three authors contributed equally to this work.): Phosphorescent Light-emitting Iridium Complexes Serve as a Hypoxia-sensing Probe for Tumor Imaging in Living Animals2010
Author(s)
Zhang, S., Hosaka, M., Yoshihara, T., Negishi, K., Iida, Y., Tobita, S., Takeuchi, T.
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Journal Title
Cancer Research
Volume: 70
Pages: 4490-4498
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[Presentation] Iridiumcomplex probes for monitoring of cellular oxygen levels and imaging of hypoxic tissues2012
Author(s)
Tobita, S., Yoshihara, T., Kobayashi, A., Ichikawa, K., Hosaka, M., Takeuchi, T
Organizer
SPIE
Place of Presentation
San Francisco
Year and Date
20120100
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