ScholarWorks Community:https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4132024-03-28T09:42:35Z2024-03-28T09:42:35ZIntracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involutionJeong, JaekwangLee, JongwonTalaia, GabrielKim, WonnamSong, JunhoHong, JuhyeonYoo, KwangminGonzalez, David G.Athonvarangkul, DianaShin, JaehunDann, PamelaHaberman, Ann M.Kim, Lark KyunFerguson, Shawn M.Choi, JungminWysolmerski, Johnhttps://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/653652024-02-06T01:30:06Z2024-12-01T00:00:00ZTitle: Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution
Authors: Jeong, Jaekwang; Lee, Jongwon; Talaia, Gabriel; Kim, Wonnam; Song, Junho; Hong, Juhyeon; Yoo, Kwangmin; Gonzalez, David G.; Athonvarangkul, Diana; Shin, Jaehun; Dann, Pamela; Haberman, Ann M.; Kim, Lark Kyun; Ferguson, Shawn M.; Choi, Jungmin; Wysolmerski, John
Abstract: Involution of the mammary gland after lactation is a dramatic example of coordinated cell death. Weaning causes distension of the alveolar structures due to the accumulation of milk, which, in turn, activates STAT3 and initiates a caspase-independent but lysosome-dependent cell death (LDCD) pathway. Although the importance of STAT3 and LDCD in early mammary involution is well established, it has not been entirely clear how milk stasis activates STAT3. In this report, we demonstrate that protein levels of the PMCA2 calcium pump are significantly downregulated within 2-4 h of experimental milk stasis. Reductions in PMCA2 expression correlate with an increase in cytoplasmic calcium in vivo as measured by multiphoton intravital imaging of GCaMP6f fluorescence. These events occur concomitant with the appearance of nuclear pSTAT3 expression but prior to significant activation of LDCD or its previously implicated mediators such as LIF, IL6, and TGF beta 3, all of which appear to be upregulated by increased intracellular calcium. We further demonstrate that increased intracellular calcium activates STAT3 by inducing degradation of its negative regulator, SOCS3. We also observed that milk stasis, loss of PMCA2 expression and increased intracellular calcium levels activate TFEB, an important regulator of lysosome biogenesis through a process involving inhibition of CDK4/6 and cell cycle progression. In summary, these data suggest that intracellular calcium serves as an important proximal biochemical signal linking milk stasis to STAT3 activation, increased lysosomal biogenesis, and lysosome-mediated cell death.2024-12-01T00:00:00ZA comprehensive characterizations of zebrafish rheotactic behaviors and its application to otoprotective drug screeningHan, EunjungChoi, Yun JaePark, SaemiRah, Yoon ChanPark, Hae-ChulLee, Sang HyunChoi, Junehttps://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/642792024-02-20T12:00:56Z2024-03-01T00:00:00ZTitle: A comprehensive characterizations of zebrafish rheotactic behaviors and its application to otoprotective drug screening
Authors: Han, Eunjung; Choi, Yun Jae; Park, Saemi; Rah, Yoon Chan; Park, Hae-Chul; Lee, Sang Hyun; Choi, June
Abstract: Aquatic animals have rheotaxis that maintains a balance in response to water flow. They sense water flow through hair cells in lateral line, thereby leading to behavior changes relevant to damages on hair cells, the primary sensory receptor cells within auditory and vestibular systems. Zebrafish are efficient animal models for high-throughput drug screening with human-like hair cells along the lateral line. Their rheotactic behaviors could be assays for hair-cell-targeted drug screening. However, knowledge and tools for rheotaxis analysis along the extent of hair-cell damage have not been fully investigated. This article aims at characterization of rheotactic behaviors identifying lateral line states via an analysis platform that simultaneously examines multiple zebrafish larvae. To this end, we developed an automated framework that incorporated animal test hardware equipment and real-time analysis software for monitoring aquatic behaviors of multiple larvae. Through this framework, a commensurable measure for one-dimensional characterization of rheotactic behaviors was consolidated so that its linear changes could be associated with the population of hair cells remaining intact. These findings satisfied requests for an automated analysis platform to conduct large-scale screening and a biomarker that discriminate the seriousness of hair cell damage to screen candidates having significant effects in otoprotective drug discovery.2024-03-01T00:00:00ZPannorin isolated from marine Penicillium sp. SG-W3: a selective monoamine oxidase A inhibitorOh, Jong MinGao, QianShin, Woong-HeeLee, Eun-YoungChung, DawoonChoi, GraceNam, Sang-JipKim, Hoonhttps://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/657772024-03-19T02:00:06Z2024-03-01T00:00:00ZTitle: Pannorin isolated from marine Penicillium sp. SG-W3: a selective monoamine oxidase A inhibitor
Authors: Oh, Jong Min; Gao, Qian; Shin, Woong-Hee; Lee, Eun-Young; Chung, Dawoon; Choi, Grace; Nam, Sang-Jip; Kim, Hoon
Abstract: Six compounds were isolated from Penicillium sp. SG-W3, a marine-derived fungus, and their inhibitory activities against target enzymes relating to neurological diseases were evaluated. Compound 1 (pannorin) was a potent and selective monoamine oxidase (MAO)-A inhibitor with a 50% inhibitory concentration (IC50) of 1.734 mu M and a selectivity index (SI) of > 23.07 versus MAO-B, and it showed an efficient antioxidant activity. All compounds showed weak inhibitory activities against acetylcholinesterase, butyrylcholinesterase, and beta-secretase. The inhibition constant (Ki) of 1 for MAO-A was 1.049 +/- 0.030 mu M with competitive inhibition. Molecular docking simulation predicted that compound 1 forms hydrogen bonds with MAO-A, and binds more tightly to MAO-A than to MAO-B (- 25.02 and - 24.06 kcal/mol, respectively). These results suggest that compound 1 is a selective, reversible, and competitive MAO-A inhibitor that can be a therapeutic candidate for treating neurological diseases.2024-03-01T00:00:00ZElectrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo studyBang, Woo-SeokHan, InboMun, Seul-AhHwang, Jong -MoonNoh, Sung HyunSon, WonsooCho, Dae-ChulKim, Byoung-JoonKim, Chi HeonChoi, HyukKim, Kyoung-Taehttps://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/658012024-03-27T02:00:08Z2024-03-01T00:00:00ZTitle: Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study
Authors: Bang, Woo-Seok; Han, Inbo; Mun, Seul-Ah; Hwang, Jong -Moon; Noh, Sung Hyun; Son, Wonsoo; Cho, Dae-Chul; Kim, Byoung-Joon; Kim, Chi Heon; Choi, Hyuk; Kim, Kyoung-Tae
Abstract: BACKGROUND CONTEXT: Electrical stimulation is a noninvasive treatment method that has gained popularity in the treatment of spinal cord injury (SCI). Activation of spinal cord -derived neural stem/progenitor cell (SC-NSPC) proliferation and differentiation in the injured spinal cord may elicit considerable neural regenerative effects. PURPOSE: This study aimed to explore the effect of electrical stimulation on the neurogenesis of SC-NSPCs. STUDY DESIGN: This study analyzed the effects of electrical stimulation on neurogenesis in rodent SC-NSPCs in vitro and in vivo and evaluated functional recovery and neural circuitry improvements with electrical stimulation using a rodent SCI model. METHODS: Rats (20 rats/group) were assigned to sham (Group 1), SCI only (Group 2), SCI + electrode implant without stimulation (Group 3), and SCI + electrode with stimulation (Group 4) groups to count total SC-NSPCs and differentiated neurons and to evaluate morphological changes in differentiated neurons. Furthermore, the Basso, Beattie, and Bresnahan scores were analyzed, and the motor- and somatosensory-evoked potentials in all rats were monitored. RESULTS: Biphasic electrical currents enhanced SC-NSPC proliferation differentiation and caused qualitative morphological changes in differentiated neurons in vitro. Electrical stimulation promoted SC-NSPC proliferation and neuronal differentiation and improved functional outcomes and neural circuitry in SCI models. Increased Wnt3, Wnt7, and b-catenin protein levels were also observed after electrical stimulation. CONCLUSIONS: Our study proved the beneficial effects of electrical stimulation on SCI. The Wnt/b-catenin pathway activation may be associated with this relationship between electrical stimulation and neuronal regeneration after SCI. CLINICAL SIGNIFICANCE: The study confirmed the benefits of electrical stimulation on SCI based on cellular, functional, electrophysiological, and histological evidence. Based on these findings, we expect electrical stimulation to make a positive and significant difference in SCI treatment strategies. (c) 2023 Published by Elsevier Inc.2024-03-01T00:00:00Z