Kazuma Aoki

Faculty of Pharmaceutical Sciences,Department of Pharmaceutical SciencesLecturer
Last Updated :2025/10/07

■Researcher basic information

Degree

  • Mar. 2003

■Career

Career

  • Apr. 2015 - Present
    Teikyo Heisei University, Faculty of Pharmaceutical Sciences
  • Aug. 2011 - Mar. 2013

■Research activity information

Paper

  • Distinguishing two distinct types of salivary extracellular vesicles: a potential tool for understanding their pathophysiological roles.
    Yuko Ogawa; Yuri Miura; Mamoru Ikemoto; Atsushi Ohnishi; Yoshikuni Goto; Kazuma Aoki; Yuki Motokurumada; Yoshihiro Akimoto; Tamao Endo; Masafumi Tsujimoto; Ryohei Yanoshita
    Frontiers in molecular biosciences, 2024
    Extracellular vesicles (EVs), which are found in almost all cells and human body fluids, are currently being studied as a source of pathophysiological information. Previously, we demonstrated that at least two types of EVs can be isolated from human whole saliva (WS) using enzymatic activity of dipeptidyl peptidase IV (DPP IV) as a marker for differentiating the EV subsets. In the present study, EV fractions, termed EV-I 20 k-ppt and EV-II 100 k-ppt, were prepared by a combination of size-exclusion chromatography of improved condition and sequential centrifugation. The EV-I 20 k-ppt fraction contained medium/large EVs with a diameter of 100-1,000 nm, including aminopeptidase N (APN), mucin 1, ezrin, and Annexin A1. EV-II 100 k-ppt contained small EVs with a diameter of 20-70 nm, with DPP IV and CD9, programmed cell death 6-interacting protein, and tumor susceptibility gene 101 as characteristic proteins. Proteomic analyses also revealed distinctive repertoires of constituent proteins. Immunoprecipitation of several membrane proteins of the EVs with respective antibodies suggested their differential local membrane environment between the two types of salivary vesicles. Thus, we identified two distinctive types of EVs, one is APN/MUC1- rich EVs (EV-I, large/medium EVs) and the other is DPP IV/CD9-rich EVs (EV-II, small EVs). Furthermore, analysis of the binding of the EVs to coronavirus spike proteins showed that EV-II 100 k-ppt, but not EV-I 20 k-ppt, significantly bound to the spike protein of Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we developed a simple method to prepare two distinctive EVs from only 1 mL of human WS using sequential immunoprecipitation. Elucidating the features and functions of these two types of salivary EVs may help us understand their pathophysiological roles in the oral cavity and gastrointestinal tract.
    DOI URL
  • Molecular and functional diversity of the oxytocinase subfamily of M1 aminopeptidases.
    Masafumi Tsujimoto; Kazuma Aoki; Yoshikuni Goto; Atsushi Ohnishi
    Journal of biochemistry, 29 Apr. 2021
    The placental leucine aminopeptidase/insulin-regulated aminopeptidase, endoplasmic reticulum aminopeptidase 1 and endoplasmic reticulum aminopeptidase 2 are part of a distinct subfamily of M1 aminopeptidases termed the 'oxytocinase subfamily'. The subfamily members show molecular diversity due to differential usage of translation initiation sites, alternative splicing and multiple single nucleotide polymorphisms. It is becoming evident that, depending on their intracellular or extracellular location, members of the oxytocinase subfamily play important roles in the maintenance of homeostasis, including the regulation of blood pressure, maintenance of normal pregnancy, retention of memory and trimming of antigenic peptides presented to major histocompatibility complex class I molecules, by acting as either aminopeptidases or binding partners of specific functional proteins in the cells. Based on their molecular diversity and moonlighting protein-like properties, it is conceivable that the subfamily members exert pleiotropic effects during evolution, to become important players in the regulation of homeostasis.
    DOI URL
  • The gene expression of two endoplasmic reticulum aminopeptidase 1 isoforms is regulated by distinct posttranscriptional mechanisms.
    Aoki K; Furuya A; Matsumoto K; Tsujimoto M
    Biochemical and biophysical research communications, Sep. 2018, [Reviewed]
    Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) is a multifunctional enzyme belonging to the M1 family of aminopeptidases and shown to be associated with various autoimmune diseases. Human ERAP1 protein has two isoforms produced by alternative splicing of the 3' terminal exon, although their functional differences have not yet been fully clarified. In this study, we showed that the isoforms undergo different posttranscriptional regulation mechanisms via their respective 3' untranslated regions. Using a reporter system, we identified several cis-elements that are important for the regulation of alternative splicing. Finally, we revealed a close relationship between the transcriptional induction of the ERAP1 gene by interferon-gamma and the alternative splicing. These results suggest that the two ERAP1 isoforms function under different pathophysiological conditions.
    DOI URL
  • MicroRNP-mediated translational activation of nonadenylated mRNAs in a mammalian cell-free system
    Motoaki Wakiyama; Koichi Ogami; Ryo Iwaoka; Kazuma Aoki; Shin-Ichi Hoshino
    Genes to Cells, 01 May 2018, [Reviewed]
    DOI URL
  • LARP1 specifically recognizes the 3' terminus of poly(A) mRNA.
    Kazuma Aoki; Shungo Adachi; Masae Homoto; Hideo Kusano; Katsuyuki Koike; Tohru Natsume
    FEBS letters, 11 Jul. 2013, [Reviewed]
    A poly(A) tail functions in mRNA turnover and in facilitating translation as a ribonucleoprotein complex with poly(A) binding proteins (PABPs). However, factors that associate with the poly(A) tail other than PABPs have not been described. Using proteomics, we identified candidate proteins that interact to the 3' terminus of the poly(A) tail. Among these proteins, we focused on La motif-related protein 1 (LARP1) and found that LARP1 specifically recognizes the 3' termini of normal poly(A) tails. We also reveal that LARP1 stabilizes multiple mRNAs carrying 5' terminal oligopyrimidine tract (5'TOP). Our findings suggest that LARP1 may be involved in the post-transcriptional regulation of gene expression, at least in several 5'TOP mRNAs, through the binding to 3' terminus of the poly(A) tail.
    DOI URL
  • A thymus-specific noncoding RNA, Thy-ncR1, is a cytoplasmic riboregulator of MFAP4 mRNA in immature T-cell lines
    Kazuma Aoki; Akira Harashima; Miho Sano; Takahide Yokoi; Shuji Nakamura; Masayoshi Kibata; Tetsuro Hirose
    BMC MOLECULAR BIOLOGY, Dec. 2010, [Reviewed]
    DOI URL
  • The NF90-NF45 Complex Functions as a Negative Regulator in the MicroRNA Processing Pathway
    Shuji Sakamoto; Kazuma Aoki; Takuma Higuchi; Hiroshi Todaka; Keiko Morisawa; Nobuyuki Tamaki; Etsuro Hatano; Atsuki Fukushima; Taketoshi Taniguchi; Yasutoshi Agata
    MOLECULAR AND CELLULAR BIOLOGY, Jul. 2009, [Reviewed]
    DOI URL
  • In vitro analyses of the production and activity of secondary small interfering RNAs in C. elegans.
    Kazuma Aoki; Hiromi Moriguchi; Tomoko Yoshioka; Katsuya Okawa; Hiroaki Tabara
    The EMBO journal, 12 Dec. 2007, [Reviewed]
    In the RNA interference (RNAi) pathway, small interfering RNAs (siRNAs) play important roles as intermediates. Primary siRNAs are produced from trigger dsRNAs by an RNaseIII-related enzyme called Dicer; in some organisms, secondary siRNAs are also produced by processes involving RNA-dependent RNA polymerases (RdRPs), which act on target mRNAs. Using a cell-free assay system prepared from Caenorhabditis elegans, we analyzed the production and activity of secondary siRNAs. In this cell-free system, RdRP activity acts on mRNA-derived templates to produce small RNAs. The RRF-1 complex is predominantly responsible for the RdRP activity, and synthesizes secondary-type siRNA molecules in a Dicer-independent manner. Notably, secondary-type siRNAs induce a prominent Slicer activity to cleave target mRNAs far more effectively than primary-type siRNAs. An Argonaute protein, CSR-1, is responsible for the Slicer activity induced by secondary-type siRNAs. Secondary rather than primary siRNAs may play a major role in the destabilization of target transcripts during RNAi in C. elegans.
  • Xenopus cold-inducible RNA-binding protein 2 interacts with ElrA, the Xenopus homolog of HuR, and inhibits deadenylation of specific mRNAs
    K Aoki; K Matsumoto; M Tsujimoto
    JOURNAL OF BIOLOGICAL CHEMISTRY, Nov. 2003, [Reviewed]
    DOI URL 2
  • Visualization of the reconstituted FRGY2-mRNA complexes by electron microscopy
    K Matsumoto; KJ Tanaka; K Aoki; M Sameshima; M Tsujimoto
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Jun. 2003, [Reviewed]
    DOI URL 2
  • Methylation of Xenopus CIRP2 regulates its arginine- and glycine-rich region-mediated nucleocytoplasmic distribution
    K Aoki; Y Ishii; K Matsumoto; M Tsujimoto
    NUCLEIC ACIDS RESEARCH, Dec. 2002, [Reviewed]
  • CIRP2, a major cytoplasmic RNA-binding protein in Xenopus oocytes
    K Matsumoto; K Aoki; N Dohmae; K Takio; M Tsujimoto
    NUCLEIC ACIDS RESEARCH, Dec. 2000, [Reviewed]
    DOI URL

MISC

Affiliated academic society

  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN