An Endonuclease Excising 8-Oxo-2'-deoxyguanosine in Regenerating Rat Liver

Oxidative DNA damage is generated in every tissue in the body, and is mainly excised by glycosylases. However, endonucleases and exonucleases are suggested as being present in tissues, since oxidized nucleosides such as thymidine glycol and 8-Oxo-2'-deoxyguanosine are detected in urine. For this reason, we studied repair enzymes induced in regenerating rat liver, and detected an enzyme cleaves phosphodiester bonds on the 5'side of 8-oxo-2'-deoxyguanosine nucleotides in DNA. The coexistence of this enzyme and phosphodiesterase II results in the release of 8-oxo-2'-deoxyguanosine monophosphate from calf thymus DNA enriched with 8-oxoguanine by γ-ray irradiation. This enzyme is found in regenerating rat liver, but not in normal rat liver. The enzyme may have a specific connection to DNA replication.DNA酸化傷害は身体中のあらゆる細胞で発生し，主にグリコシラーゼ類によって除去されている．しかし，チミジングリコールや8-オキソ-2’-デオキシグアノシンのような酸化ヌクレオシドも尿中に排泄されてきて検出されるので，エンドヌクレアーゼとエキソヌクレアーゼが組織中に存在することが示唆される．本研究は複製が活発に行われる再生肝を用いて，エンドヌクレアーゼ活性を持つ修復酵素をホスホセルロースカラムによって分離して検出することを試みた．その結果，再生肝中にDNA中の8-オキソ-2’-デオキシグアノシンヌクレオシドの5’側のホスホジエステル結合を切断する活性があることが判明した．本酵素とホスホジエステラーゼを共存させると，γ-線を照射して8-オキソグアニンを豊富に含む子ウシ胸腺DNAから，8-オキソ-2’-デオキシグアノシンが放出された．本酵素はラット再生肝では認められたが，通常のラット肝では認められなかった．本酵素は，DNA複製と特異的に関連しているのかもしれない

Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan

Hydrogen Isotope (H2 and D2) Sorption Study of CHA-Type Zeolites

Using either single H2 and D2 or H2-D2 mixed gases, the sorption abilities of CHA (chabazite)-type zeolites ion-exchanged with K, Na, or Ca were studied at 77, 201, and 250 K. The LTA (Linde Type A) (3A) and FAU (faujasite)-type zeolites were also examined for comparison. The pore diameters in these materials were found to decrease on the order of FAU > Ca-CHA > [K-CHA, Na-CHA, and LTA(3A)]. The quantities of D2 adsorbed on these zeolites were larger than the amounts of H2. At higher temperatures, the CHA-type zeolites having smaller pores exhibited superior D2/H2 selectivity compared with the LTA(3A) and FAU, suggesting that hydrogen isotope separation using zeolites is affected by pore size

An Endonuclease Excising 8-Oxo-2'-deoxyguanosine in Regenerating Rat Liver

Oxidative DNA damage is generated in every tissue in the body, and is mainly excised by glycosylases. However, endonucleases and exonucleases are suggested as being present in tissues, since oxidized nucleosides such as thymidine glycol and 8-Oxo-2'-deoxyguanosine are detected in urine. For this reason, we studied repair enzymes induced in regenerating rat liver, and detected an enzyme cleaves phosphodiester bonds on the 5'side of 8-oxo-2'-deoxyguanosine nucleotides in DNA. The coexistence of this enzyme and phosphodiesterase II results in the release of 8-oxo-2'-deoxyguanosine monophosphate from calf thymus DNA enriched with 8-oxoguanine by γ-ray irradiation. This enzyme is found in regenerating rat liver, but not in normal rat liver. The enzyme may have a specific connection to DNA replication.DNA酸化傷害は身体中のあらゆる細胞で発生し，主にグリコシラーゼ類によって除去されている．しかし，チミジングリコールや8-オキソ-2’-デオキシグアノシンのような酸化ヌクレオシドも尿中に排泄されてきて検出されるので，エンドヌクレアーゼとエキソヌクレアーゼが組織中に存在することが示唆される．本研究は複製が活発に行われる再生肝を用いて，エンドヌクレアーゼ活性を持つ修復酵素をホスホセルロースカラムによって分離して検出することを試みた．その結果，再生肝中にDNA中の8-オキソ-2’-デオキシグアノシンヌクレオシドの5’側のホスホジエステル結合を切断する活性があることが判明した．本酵素とホスホジエステラーゼを共存させると，γ-線を照射して8-オキソグアニンを豊富に含む子ウシ胸腺DNAから，8-オキソ-2’-デオキシグアノシンが放出された．本酵素はラット再生肝では認められたが，通常のラット肝では認められなかった．本酵素は，DNA複製と特異的に関連しているのかもしれない

Mutations in the β-amyloid precursor protein in familial Alzheimer’s disease increase Aβ oligomer production in cellular models

Soluble oligomers of amyloid-β (Aβ) peptides (AβOs) contribute to neurotoxicity in Alzheimer’s disease (AD). However, it currently remains unknown whether an increase in AβOs is the common phenotype in cellular and animal models. Furthermore, it has not yet been established whether experimental studies conducted using models overexpressing mutant genes of the amyloid precursor protein (APP) are suitable for investigating the underlying molecular mechanism of AD. We herein employed the Flp-In™ T-REx™-293 (T-REx 293) cellular system transfected with a single copy of wild-type, Swedish-, Dutch-, or London-type APP, and quantified the levels of Aβ monomers (Aβ1-40 and Aβ1-42) and AβOs using an enzyme-linked immunosorbent assay (ELISA). The levels of extracellular AβOs were significantly higher in Dutch- and London-type APP-transfected cells than in wild-type APP-transfected cells. Increased levels were also observed in Swedish-type APP-transfected cells. On the other hand, intracellular levels of AβOs were unaltered among wild-type and mutant APP-transfected cells. Intracellular levels of Aβ monomers were undetectable, and no common abnormality was observed in their extracellular levels or ratios (Aβ1-42/Aβ1-40) among the cells examined. We herein demonstrated that increased levels of extracellular AβOs are the common phenotype in cellular models harboring different types of APP mutations. Our results suggest that extracellular AβOs play a key role in the pathogenesis of AD