Age-related Asp Isomerizations in Lens Alpha-crystallin

• Project/Area Number: 15K16514
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Kyoto University (2016); Tokyo University of Pharmacy and Life Science (2015)
• Principal Investigator: Takata Takumi 京都大学, 原子炉実験所, 特定准教授 (80379007)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: D-アミノ酸 / クリスタリン / 白内障 / 加齢 / タンパク質異常凝集 / 質量分析 / D-Asp / 水晶体 / crystallin / タンパク質

Outline of Final Research Achievements

The lens α-crystallin is composed of two subunits αA- and αB-crystallin (αA-Crys and αB-Crys), which form various oligomers and complexes. Recent studies have shown that many aspartyl residues (Asp) in αA-Crys inverted to isomers (Lβ-Asp, Dα-Asp, Dβ-Asp) with age. It has not been well understood whether Asp isomers in native polymeric αA-Crys are different from those in dissociated αA-Crys or those in aggregated complexes. We therefore examined to clarify the distribution of Asp isomers in dissociated αA-Crys and those in aggregated αA-Crys. The results showed that the isomerization of Asp 58 in αA-Crys were highly detectable from the monomeric fraction. In addition, age-dependent Asp 58 isomerization in α-Crys is similar to the ratio from lens insoluble fraction. The isomerization of Asp as well as many other modifications would reduce the normal subunit-subunit interaction of α-Crys with aging, result in senile cataract formation.

Research Products

• [Journal Article] Ferulic Acid Suppresses Amyloid β Production in the Human Lens Epithelial Cell Stimulated with Hydrogen Peroxide. (2017)
  • Author(s): Nagai N, Kotani S, Mano Y, Ueno A, Ito Y, Kitaba T, Takata T and Fujii N.
  • Journal Title: Biomed. Res. Int. Volume: - Pages: 1-9
  • DOI: 10.1155/2017/5343010
  • Peer Reviewed / Open Access
• [Journal Article] Isomeric Replacement of a Single Aspartic Acid Induces a Marked Change in Protein Function: The Example of Ribonuclease A (2017)
  • Author(s): Sakaue H, Kinouchi T, Fujii N, Takumi T, Fujii N.
  • Journal Title: ACS Omega Volume: 2 Issue: 1 Pages: 260-267
  • DOI: 10.1021/acsomega.6b00346
  • Peer Reviewed / Open Access
• [Journal Article] Aggregation of Trp > Glu point mutants of human gamma-D crystallin provides a model for hereditary or UV-induced cataract. (2016)
  • Author(s): Serebryany E, Takata T, Erickson E, Schafheimer N, Wang Y, King JA.
  • Journal Title: Protein science. Volume: 6 Issue: 6 Pages: 1115-1128
  • DOI: 10.1002/pro.2924
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] New insight into the dynamical system of αB-crystallin oligomers (2016)
  • Author(s): R. Inoue, T. Takata, N. Fujii, K. Ishii, S. Uchiyama, N. Sato, Y. Oba, K. Wood, K. Kato, N. Fujii, and M. Sugiyama
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 29208-29208
  • DOI: 10.1038/srep29208
  • NAID: 120006323745
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Isomerization of Asp residues plays an important role in αA-crystallin dissociation. (2016)
  • Author(s): Takata T, Fujii N.
  • Journal Title: FEBS J. Volume: 283 Issue: 5 Pages: 850-859
  • DOI: 10.1111/febs.13635
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effect of Asp 96 isomerization on the properties of a lens αB-crystallin-derived short peptide. (2015)
  • Author(s): Takata T, Fujii N.
  • Journal Title: J Pharm Biomed Anal. Volume: 116 Pages: 139-144
  • DOI: 10.1016/j.jpba.2015.06.017
  • Peer Reviewed
• [Presentation] Age-related abnormal Asp isomers distribution in lens specific αA-crystallin monomeric and polymeric state (2017)
  • Author(s): Takumi Takata and Noriko Fujii
  • Organizer: The 3rd International Conference of D-Amino Acid Research
  • Place of Presentation: Varese, Italy
  • Year and Date: 2017-07-10
  • Int'l Joint Research / Invited
• [Presentation] Age-related abnormal Asp isomers distribution in lens specific αA-crystallin monomeric and polymeric state (2016)
  • Author(s): Takumi Takata, Takashi Sato, Hiroshi Sasaki and Noriko Fujii
  • Organizer: XXII Biennial Meeting of the International Society for Eye Research
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2016-09-25
  • Int'l Joint Research / Invited
• [Presentation] Age-related Asp Isomerization in Dissociated Alpha-crystallin from Aged Lens (2016)
  • Author(s): Takumi Takata, Takashi Sato, Noriko Fujii
  • Organizer: ARVO 2016
  • Place of Presentation: Seattle, USA
  • Year and Date: 2016-04-30
  • Int'l Joint Research
• [Presentation] Isomerization of Asp residues is different between monomer and hetero-polymer of alpha-crystallin in aged human lens. (2015)
  • Author(s): T. Takata and N Fujii.
  • Organizer: International Conference on the Lens 2015.
  • Place of Presentation: Kona, USA
  • Year and Date: 2015-12-06
  • Int'l Joint Research
• [Presentation] 加齢後のヒト水晶体内におけるαA-クリスタリン単量体内と会合体内のAsp異性化率の相違 (2015)
  • Author(s): 高田匠, 藤井紀子
  • Organizer: 第11回D-アミノ酸学会
  • Place of Presentation: 長岡
  • Year and Date: 2015-09-14