Bae KH

References (4)

Title : The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism - Oh_2023_Nat.Commun_14_5728
Author(s) : Oh M , Jang SY , Lee JY , Kim JW , Jung Y , Kim J , Seo J , Han TS , Jang E , Son HY , Kim D , Kim MW , Park JS , Song KH , Oh KJ , Kim WK , Bae KH , Huh YM , Kim SH , Han BS , Lee SC , Hwang GS , Lee EW
Ref : Nat Commun , 14 :5728 , 2023
Abstract : Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment.
ESTHER : Oh_2023_Nat.Commun_14_5728
PubMedSearch : Oh_2023_Nat.Commun_14_5728
PubMedID: 37714840

Title : A lactate-induced response to hypoxia - Lee_2015_Cell_161_595
Author(s) : Lee DC , Sohn HA , Park ZY , Oh S , Kang YK , Lee KM , Kang M , Jang YJ , Yang SJ , Hong YK , Noh H , Kim JA , Kim DJ , Bae KH , Kim DM , Chung SJ , Yoo HS , Yu DY , Park KC , Yeom YI
Ref : Cell , 161 :595 , 2015
Abstract : Organisms must be able to respond to low oxygen in a number of homeostatic and pathological contexts. Regulation of hypoxic responses via the hypoxia-inducible factor (HIF) is well established, but evidence indicates that other, HIF-independent mechanisms are also involved. Here, we report a hypoxic response that depends on the accumulation of lactate, a metabolite whose production increases in hypoxic conditions. We find that the NDRG3 protein is degraded in a PHD2/VHL-dependent manner in normoxia but is protected from destruction by binding to lactate that accumulates under hypoxia. The stabilized NDRG3 protein binds c-Raf to mediate hypoxia-induced activation of Raf-ERK pathway, promoting angiogenesis and cell growth. Inhibiting cellular lactate production abolishes the NDRG3-mediated hypoxia responses. Our study, therefore, elucidates the molecular basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases.
ESTHER : Lee_2015_Cell_161_595
PubMedSearch : Lee_2015_Cell_161_595
PubMedID: 25892225

Title : Identification of proteins binding to decursinol by chemical proteomics - Kang_2008_J.Microbiol.Biotechnol_18_1427
Author(s) : Kang HJ , Yoon TS , Jeong DG , Kim Y , Chung JW , Ha JS , Park SS , Ryu SE , Kim S , Bae KH , Chung SJ
Ref : J Microbiol Biotechnol , 18 :1427 , 2008
Abstract : Decursinol, found in the roots of Angelica gigas Nakai, has been traditionally used to treat anemia and other various diseases. Recently, numerous biological activities such as cytotoxic effect on leukemia cells, and antitumor, neuroprotection, and antibacterial activities have been reported for this compound. Although a number of proteins including protein kinase C, androgen receptor, and acetylcholinesterase were proposed as molecular targets responsible for the activities of decursinol, they are not enough to explain such a diverse biological activity mentioned above. In this study, we employed a chemical proteomic approach, leading to identification of seven proteins as potential proteins interacting with decursinol. Most of the proteins contain a defined ATP or nucleic acid binding domain and have been implied to be involved in the pathogenesis and progression of various human diseases including cancer, autoimmune disorders, or neurodegenerative diseases. The present results may provide clues to understand the molecular mechanism of the biological activities shown by decursinol, an anticancer natural product.
ESTHER : Kang_2008_J.Microbiol.Biotechnol_18_1427
PubMedSearch : Kang_2008_J.Microbiol.Biotechnol_18_1427
PubMedID: 18756104

Title : Gomisin A improves scopolamine-induced memory impairment in mice - Kim_2006_Eur.J.Pharmacol_542_129
Author(s) : Kim DH , Hung TM , Bae KH , Jung JW , Lee S , Yoon BH , Cheong JH , Ko KH , Ryu JH
Ref : European Journal of Pharmacology , 542 :129 , 2006
Abstract : Gomisin A is a component of the fruits of Schizandra chinesis which are widely used as a tonic in traditional Chinese medicine. In the present study, we assessed the effect of gomisin A on the learning and memory impairments induced by scopolamine. The cognition-enhancing effect of gomisin A was investigated using a passive avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug-induced amnesia was induced by treating animals with scopolamine (1 mg/kg, i.p.). Gomisin A (5 mg/kg, p.o.) administration significantly reversed scopolamine-induced cognitive impairments in mice by the passive avoidance test and the Y-maze test (P<0.05), and also improved escape latency in the Morris water maze test at 5 mg/kg (P<0.05). Moreover, in an in vitro study, gomisin A was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC50 value; 15.5 microM). These results suggest that gomisin A may be a useful cognitive impairment treatment, and its beneficial effects are mediated, in part, via enhancing the cholinergic nervous system.
ESTHER : Kim_2006_Eur.J.Pharmacol_542_129
PubMedSearch : Kim_2006_Eur.J.Pharmacol_542_129
PubMedID: 16824513