The University of Osaka · Medicine
타모츠 요시모리 교수의 연구실은 세포의 자가분해 과정인 자가포식(autophagy)이 병원성 박테리아 등 병원체에 대한 면역 방어 기전으로 작용하는 메커니즘을 규명하고 있습니다. 특히 자가포식이 림프구나 전형적 면역세포 외에도 비포식세포에서도 병원체를 제거하는 중요한 역할을 한다는 점을 밝혀내었으며, 이 과정에서 리소좀의 산성 환경 유지를 위한 H+-ATPase 기능과 관련된 약물 작용 메커니즘도 연구하고 있습니다. 또한 자가포식 억제와 관련된 단백질인 Rubicon이 간지방증(NAFLD)의 발병 메커니즘에서 핵심적으로 작용함을 규명하며, 자가포식 조절이 대사질환 치료의 새로운 타겟이 될 수 있음을 제시하고 있습니다.
Figures are computed from collected data and may differ slightly.
Bafilomycin A1 is known as a strong inhibitor of the vacuolar type H(+)-ATPase in vitro, whereas other type ATPases, e.g. F1,F0-ATPase, are not affected by this antibiotic (Bowman, E.M., Siebers, A., and Altendorf, K. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7972-7976). Effects of this inhibitor on lysosomes of living cultured cells were tested. The acidification of lysosomes revealed by the incubation with acridine orange was completely inhibited when BNL CL.2 and A431 cells were treated with 0
We found that the autophagic machinery could effectively eliminate pathogenic group A Streptococcus (GAS) within nonphagocytic cells. After escaping from endosomes into the cytoplasm, GAS became enveloped by autophagosome-like compartments and were killed upon fusion of these compartments with lysosomes. In autophagy-deficient Atg5-/- cells, GAS survived, multiplied, and were released from the cells. Thus, the autophagic machinery can act as an innate defense system against invading pathogens.
Rubicon is overexpressed and plays a pathogenic role in NAFLD by accelerating hepatocellular lipoapoptosis and lipid accumulation, as well as inhibiting autophagy. Rubicon may be a novel therapeutic target for regulating NAFLD development and progression. (Hepatology 2016;64:1994-2014).
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