The regulation of soluble receptor for AGEs contributes to carbonyl stress in schizophrenia

Mitsuhiro Miyashita, Takuo Watanabe, Tomoe Ichikawa, Kazuya Toriumi, Yasue Horiuchi, Akiko Kobori, Itaru Kushima, Ryota Hashimoto, Motoyuki Fukumoto, Shinsuke Koike, Hiroshi Ujike, Tadao Arinami, Yoshitaka Tatebayashi, Kiyoto Kasai, Masatoshi Takeda, Norio Ozaki, Yuji Okazaki, Takeo Yoshikawa, Naoji Amano, Shinsuke WashizukaHiroshi Yamamoto, Toshio Miyata, Masanari Itokawa, Yasuhiko Yamamoto, Makoto Arai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Our previous study showed that enhanced carbonyl stress is closely related to schizophrenia. The endogenous secretory receptor for advanced glycation end-products (esRAGE) is a splice variant of the AGER gene and is one of the soluble forms of RAGE. esRAGE is considered to be a key molecule for alleviating the burden of carbonyl stress by entrapping advanced glycation end-products (AGEs). In the current study, we conducted genetic association analyses focusing on AGER, in which we compared 212 schizophrenic patients to 214 control subjects. We also compared esRAGE levels among a subgroup of 104 patients and 89 controls and further carried out measurements of total circulating soluble RAGE (sRAGE) in 25 patients and 49 healthy subjects. Although the genetic association study yielded inconclusive results, multiple regression analysis indicated that a specific haplotype composed of rs17846798, rs2071288, and a 63 bp deletion, which were in perfect linkage disequilibrium (r2 = 1), and rs2070600 (Gly82Ser) were significantly associated with a marked decrease in serum esRAGE levels. Furthermore, compared to healthy subjects, schizophrenia showed significantly lower esRAGE (p = 0.007) and sRAGE (p = 0.03) levels, respectively. This is the first study to show that serum esRAGE levels are regulated by a newly identified specific haplotype in AGER and that a subpopulation of schizophrenic patients are more vulnerable to carbonyl stress.

Original languageEnglish
Pages (from-to)447-452
Number of pages6
JournalBiochemical and biophysical research communications
Volume479
Issue number3
DOIs
Publication statusPublished - 2016 Oct 21

Keywords

  • Advanced glycation end-products (AGEs)
  • Carbonyl stress
  • Endogenous secretory RAGE (esRAGE)
  • Receptor for AGEs (RAGE)
  • Schizophrenia
  • Soluble RAGE (sRAGE)

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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