NAIST 奈良先端科学技術大学院大学 バイオサイエンス領域

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1) Emerging roles of CAMSAPs on lung cancer aggressiveness
2) Neferine exerts neuroprotective effects in a rat model of cerebral ischemia through autophagy pathway

演題 1) Emerging roles of CAMSAPs on lung cancer aggressiveness
2) Neferine exerts neuroprotective effects in a rat model of cerebral ischemia through autophagy pathway
講演者 1) Dr. Varisa Pongrakhananon (Chulalongkorn University Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences)
2) Dr. Jiraporn Tocharus (Chiang Mai University Department of Physiology)
使用言語 English
日時 2021年2月17日(水曜日) 10:30~12:30
場所 Zoom (Please contact Kanai-sensei at kanai@bs.naist.jp (internal 5474) for access.)
内容

1) Due to the high death rate of lung cancer, the discovery of new molecular target is remaining challenged. A cancer microarray database has reported that calmodulin-regulated spectrin-associated proteins (CAMSAPs) express differently between lung cancer and normal lung epithelial cells, and among stages of lung cancer. CAMSAP family proteins, consisted of CAMSAP-1, -2 and -3, bind to and stabilize minus-end of noncentrosomal microtubules. CAMSAPs have been reported to play a physiological role on tissue organization and neuronal development. However, role of CAMSAPs on lung cancer biology are remaining unknown. Here, we discover that CAMSAP3 depletion by CRISPR-Cas9 system enhances cell migration through epithelial-to-mesenchymal transition (EMT) mechanism. Tubulin acetylation is substantially raised that sustains Akt activity, an oncogenic-driven pathway, and consequently promotes EMT-regulatory protein expressions. CAMSAP3 knockout also mediates cellular senescence, an aging cellular response characterized by an irreversible growth arrest, via ERK inhibition. Proteomic analysis revealed that vimentin, an intermediate filament protein, is a possible scaffold protein for CAMSAP3-regulating ERK signaling. In contrast, CAMSAP2 exhibits a tumor-suppressing effect including abrogates lung cancer cell motility. The molecular mechanism and clinical investigation of CAMSAPs will be further explored to strengthen the oncogenic functions and its potential application.

2) Neferine is the major alkaloid compound isolated from the seed embryos of lotus. Neferine has many pharmacological effects such as antiinflammation, anti-oxidative stress, and anti-apoptosis, and it maintains autophagic balance. The purpose of this study was to explore the mechanism by which neferine attenuates autophagy after permanent cerebral ischemia in rats. We performed permanent cerebral ischemia in rats by middle cerebral artery occlusion (pMCAO) for 12 h with or without administration of neferine or a calcium (Ca2+) channel blocker (nimodipine). Neuroprotective effects were determined by evaluating the infarct volume and neurological deficits. Autophagy and it signaling pathway were determined by evaluating the expression of phosphorylated AMP-activated protein kinase alpha (AMPKα), phosphorylated mammalian target of rapamycin (mTOR), beclin-1, microtubule-associated protein 1A/1B-light chain 3 class II (LC3-II), and p62 by western blotting. The autophagosome was evaluated by transmission electron microscopy. Neferine treatment significantly reduced infarct volumes and improved neurological deficits. Neferine significantly attenuated the upregulation of autophagy-associated proteins such as LC3-II, beclin-1, and p62 as well as autophagosome formation, all of which were induced by pMCAO. Neferine exerted remarkable protection against cerebral ischemia, possibly via the inhibition of autophagy mediated by the Ca2+-dependent AMPK/mTOR pathway.

問合せ先
Kenichi Kanai (kanai@bs.naist.jp)

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