KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats

Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA

Antarctic Cryosphere Evolution Project (AnCEP): New IODP proposal for transect drilling in the Southern Ocean

第3回極域科学シンポジウム　横断セッション「海・陸・氷床から探る後期新生代の南極寒冷圏環境変動」11月26日（月） 国立国語研究所 ２階講

A Histone-Like Protein of Mycobacteria Possesses Ferritin Superfamily Protein-Like Activity and Protects against DNA Damage by Fenton Reaction

Iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the Fenton reaction. In addition, ferric ion shows low solubility under physiological conditions. To overcome these obstacles living organisms possess Ferritin superfamily proteins that are distributed in all three domains of life: bacteria, archaea, and eukaryotes. These proteins minimize hydroxyl radical formation by ferroxidase activity that converts Fe2+ into Fe3+ and sequesters iron by storing it as a mineral inside a protein cage. In this study, we discovered that mycobacterial DNA-binding protein 1 (MDP1), a histone-like protein, has similar activity to ferritin superfamily proteins. MDP1 prevented the Fenton reaction and protects DNA by the ferroxidase activity. The Km values of the ferroxidase activity by MDP1 of Mycobacterium bovis bacillus Calmette-Guérin (BCG-3007c), Mycobacterium tuberculosis (Rv2986c), and Mycobacterium leprae (ML1683; ML-LBP) were 0.292, 0.252, and 0.129 mM, respectively. Furthermore, one MDP1 molecule directly captured 81.4±19.1 iron atoms, suggesting the role of this protein in iron storage. This study describes for the first time a ferroxidase-iron storage protein outside of the ferritin superfamily proteins and the protective role of this bacterial protein from DNA damage

Draft genome sequence of Colletotrichum sansevieriae Sa-1–2, the anthracnose pathogen of Sansevieria trifasciata

Colletotrichum sansevieriae is an ascomycete fungus causing anthracnose disease on plants in the genus Sansevieria. Here, we report the draft genome sequence of isolate Sa-1–2 of this fungus. The genome size is >51 Mb, and the assembly consists of 8647 contigs and contains 13,664 predicted protein-coding genes. Pathogenicity factors such as plant cell wall-degrading enzymes and effector proteins were also predicted. Additionally, the phylogenetic relationship of isolates from different Colletotrichum spp. was analyzed, revealing that the isolate belongs to a novel major clade consisting of species that infect succulent plants originating from Africa. The draft genome sequence has been deposited at GenBank under accession number NJHP00000000