The role of lipid droplets in the steroid hormone synthesis in MLTC-1 mouse Leydig tumor cells.

• Project/Area Number: 23790098
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Showa University
• Principal Investigator: YAMAGUCHI Tomohiro 昭和大学, 薬学部, 准教授 (50347530)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 脂肪滴 / 細胞小器官 / 脂質代謝 / 細胞生物学 / 生化学 / 脂質生化学 / ステロイドホルモン

Research Abstract

Lipid droplets (LDs) are functional subcellular organelles involved in multiple intracellular processes. Although LDs are found in nearly all types of eukaryotic cells, their properties are highly variable among tissues.
Steroidogenic cells normally accumulate numerous small cytosolic LDs, but the profiles of LD-associated proteins and the biological significance of these remains unclear. I found that LD fraction from mouse leydig tumor (MLTC-1) cells, abundantly contains the enzymes for steroidogenesis, especially 3beta-HSD1 and 17beta-HSD11 and the activation of steroidgenesis by luteinizing hormone (LH) caused drastic change in morphology of LDs. Upon stimulation, perinuclear LDs are changed into relatively nascent LDs and possibly fused to ER. I next studied about the LDs of HL-60-derived neutrophils and found that perilipin-3 (PLIN3) has a pivotal role in LD-biogenesis, and that PLIN3 is associated with the synthesis and secretion of PGE2.

Research Products

• [Journal Article] Crucial role of perilipin-3 (TIP47) in formation of lipid droplets and PGE2 production in HL-60-derived neutrophils. (2013)
  • Author(s): Nose F, Yamaguchi T, Kato R, Aiuchi T, Obama T, Hara S, Yamamoto M, Itabe H.
  • Journal Title: PLoS One. Volume: 8 Issue: 8 Pages: 71542-71542
  • DOI: 10.1371/journal.pone.0071542
  • Peer Reviewed
• [Journal Article] Active involvement of micro-lipid droplets and lipid droplet-associated proteins in hormone-stimulated lipolysis in adipocytes (2012)
  • Author(s): Hashimoto T, Segawa H, Okuno M, Kano H, Hamaguchi HO, Haraguchi T, Hiraoka Y, Hasui S, Yamaguchi T, Hirose F, Osumi T
  • Journal Title: J Cell Sci Volume: 125 Pages: 6127-6136
  • Peer Reviewed
• [Journal Article] (*Equal Contribution) Perilipin 5, a Lipid Droplet-binding Protein, Protects Heart from Oxidative Burden by Sequestering Fatty Acid from Excessive Oxidation (2012)
  • Author(s): Kuramoto K, Okamura T, Yamaguchi T, Nakamura TY, Wakabayashi S, Morinaga H, Nomura M, Yanase T, Otsu K, Usuda N, Matsumura S, Inoue K, Fushiki T, Kojima Y, Hashimoto T, Sakai F, Hirose F, Osumi T
  • Journal Title: J Biol Chem Volume: 287 Pages: 23852-23863
  • Peer Reviewed
• [Journal Article] Perilipin 5, a lipid droplet-binding protein, protects the heart from oxidative damage by preventing excess fatty acid oxidation (2012)
  • Author(s): Kuramoto K, Okamura T, Yamaguchi T, Nakamura TY, et.al.
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 28 Pages: 23852-63
  • DOI: 10.1074/jbc.m111.328708
  • Peer Reviewed
• [Journal Article] Active involvement of micro-lipid droplets and lipiddroplet-associated proteins in hormone-stimulated lipolysis in adipocytes (2012)
  • Author(s): Hashimoto T, Segawa H, Okuno M, Kano H, Hamaguchi HO, Haraguchi T, Hiraoka Y, Hasui S, Yamaguchi T, Hirose F, Osumi T
  • Journal Title: Journal of Cell Science Volume: 125(24) Issue: 24 Pages: 6127-6136
  • DOI: 10.1242/jcs.113084
  • Peer Reviewed
• [Journal Article] Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein (2011)
  • Author(s): Wang H, Bell M, Sreenevasan U, Hu H, Liu J, Dalen K, Londos C, Yamaguchi T, Rizzo MA, Coleman R, Gong D, Brasaemle D, Sztalryd C
  • Journal Title: J Biol Chem Volume: 286 Pages: 15707-15715
  • Peer Reviewed
• [Journal Article] Dietary cholesterol reduces plasma triacylglycerol in apolipoprotein E-null mice : Suppression of lipin-1 and -2 in the glycerol-3-phosphate (2011)
  • Author(s): Takashi Obama, et al
  • Journal Title: PLoS ONE Volume: 6 Issue: 8 Pages: 22917-22917
  • DOI: 10.1371/journal.pone.0022917
  • Peer Reviewed
• [Journal Article] Oxidized low-density lipoprotein-induced periodontal inflammation is associated with the up-regulation of cyclooxygenase -2 and microsomal prostaglandin synthase 1 in human gingival epithelial cells (2011)
  • Author(s): Nagahama Y, Obama T, Usui M, Kanazawa Y, Iwamoto S, Suzuki K, Miyazaki A, Yamaguchi T, Yamamoto M, Itabe H
  • Journal Title: Biochem Biophys Res Commun Volume: 413 Pages: 566-571
  • Peer Reviewed
• [Journal Article] Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein. (2011)
  • Author(s): Wang, H
  • Journal Title: J Biol Chem Volume: 286 Issue: 18 Pages: 15707-15715
  • DOI: 10.1074/jbc.m110.207779
  • Peer Reviewed
• [Journal Article] Oxidized low density lipoprotein-induced periodontal inflammation is associated with up-regulation of cyclooxygenase-2 and microsomal prostaglandin synthase 1 in human gingival epithelial cells (2011)
  • Author(s): Yu Nagahama, et al
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 413 Issue: 4 Pages: 566-571
  • DOI: 10.1016/j.bbrc.2011.09.002
  • Peer Reviewed
• [Presentation] ヒト間葉系幹細胞(hMSC)由来の脂肪細胞の分化に関する研究 (2014)
  • Author(s): 二村哲未,山口智広,上原弥未,菅井瞳,猪砂絵美,橘洋介,渕上圭子,中西里奈,笹部直子,加藤里奈,板部洋之
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 熊本
  • Year and Date: 2014-03-28
• [Presentation] Perilipin-3/TIP47はHL-60由来好中球における脂肪滴の形成とプロスタグランジンE_2の産生に関与する (2013)
  • Author(s): 野瀬冬樹、山口智広、相内敏弘、小浜孝士、加藤里奈、山本松男、板部洋之
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-09-12
• [Presentation] HL-60好中球においてPerilipin-3/TIP47は脂肪滴形成とプロスタグランジンE_2産生に関与する (2013)
  • Author(s): 野瀬冬樹、山口智広、相内敏弘、小浜孝士、加藤里奈、山本松男、板部洋之
  • Organizer: 第55回脂質生化学会
  • Place of Presentation: 松島
  • Year and Date: 2013-06-07
• [Presentation] Perilipin-3/TIP47はHL-60由来好中球における脂肪滴の形成とプロスタグランジンE2の産生に関与する (2013)
  • Author(s): 野瀬冬樹、○山口智広、相内敏弘、小浜孝士、加藤里奈、山本松男、板部洋之
  • Organizer: 日本生化学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] HL-60好中球においてPerilipin-3/TIP47は脂肪滴形成とプロスタグランジンE2産生に関与する (2013)
  • Author(s): 野瀬冬樹、○山口智広、相内敏弘、小浜孝士、加藤里奈、山本松男、板部洋之
  • Organizer: 脂質生化学会
  • Place of Presentation: ホテル松島大観荘（宮城県宮城郡）
• [Presentation] 細胞内脂肪滴における中性脂肪の蓄積と分解の制御機構 (2012)
  • Author(s): 山口智広
  • Organizer: 第56回日本薬学会関東支部大会
  • Place of Presentation: 品川
  • Year and Date: 2012-10-13
• [Presentation] マウスライディッヒ細胞株(MLTC-1)における脂肪滴タンパク質の機能解析 (2012)
  • Author(s): 山口智広、藤川典之、長澤充、櫻井敦史、小浜孝士、加藤里奈、板部洋之
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-29
• [Presentation] 細胞内脂肪滴における中性脂肪の蓄積と分解の制御機構 (2012)
  • Author(s): 山口智広
  • Organizer: 第56回 日本薬学会関東支部大会
  • Place of Presentation: 昭和大学
  • Invited
• [Presentation] MLTC-1細胞のステロイドホルモン産生に伴う脂肪滴の形態変化 (2012)
  • Author(s): 山口智広
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学（札幌）
• [Presentation] The role of lipid droplets in the steroid hormone synthesis in Leydig cells (2011)
  • Author(s): Tomohiro Yamaguchi
  • Organizer: The 30th Naito Conference on Membrane Dynamics and Lipid Biology[II]
  • Place of Presentation: 札幌
  • Year and Date: 2011-06-29
• [Presentation] ステロイド産生細胞(MLTC-1)における脂肪滴局在タンパク質の解析 (2011)
  • Author(s): 山口智広、藤川典之、相内敏弘、津田園佳、徳岡雄太郎、二村哲未、小浜孝士、加藤里奈、板部洋之
  • Organizer: 第53回脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-12
• [Presentation] The role of lipid droplets in the steroid hormone synthesis in Leydig cells (2011)
  • Author(s): 山口智広
  • Organizer: The 30th Naito Conference on Membrane Dynamics and Lipid Biology[II]
  • Place of Presentation: シャトレーゼガトーキングダム（札幌）
• [Remarks] 薬学部生体分子薬学講座 生物化学部門
  • URL: http://www.showa-u.ac.jp/sch/pharm/major/biolchem/index.html