PLOS ONE: [sortOrder=DATE_NEWEST_FIRST, from=authorLink, sort=Relevance, q=author:"Jeong-Han Lee"]PLOShttps://journals.plos.org/plosone/webmaster@plos.orgaccelerating the publication of peer-reviewed sciencehttps://journals.plos.org/plosone/search/feed/atom?sortOrder=DATE_NEWEST_FIRST&unformattedQuery=author:%22Jeong-Han%20Lee%22&from=authorLink&sort=RelevanceAll PLOS articles are Open Access.https://journals.plos.org/plosone/resource/img/favicon.icohttps://journals.plos.org/plosone/resource/img/favicon.ico2024-03-29T09:11:11ZAssociation of Reduced Folate Carrier-1 (RFC-1) Polymorphisms with Ischemic Stroke and Silent Brain InfarctionYunkyung ChoJung O KimJeong Han LeeHye Mi ParkYoung Joo JeonSeung Hun OhJinkun BaeYoung Seok ParkOk Joon KimNam Keun Kim10.1371/journal.pone.01152952015-02-06T14:00:00Z2015-02-06T14:00:00Z<p>by Yunkyung Cho, Jung O Kim, Jeong Han Lee, Hye Mi Park, Young Joo Jeon, Seung Hun Oh, Jinkun Bae, Young Seok Park, Ok Joon Kim, Nam Keun Kim</p>
Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known <i>RFC-1</i> polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three <i>RFC-1</i> polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the <i>RFC-1</i> -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The <i>RFC-1</i> 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the <i>RFC-1</i> -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.(-)-Epigallocatechin-3-Gallate Protects against NO-Induced Ototoxicity through the Regulation of Caspase- 1, Caspase-3, and NF-κB ActivationSu-Jin KimJeong-Han LeeBeom-Su KimHong-Seob SoRaekil ParkNoh-Yil MyungJae-Young UmSeung-Heon Hong10.1371/journal.pone.00439672012-09-28T14:00:00Z2012-09-28T14:00:00Z<p>by Su-Jin Kim, Jeong-Han Lee, Beom-Su Kim, Hong-Seob So, Raekil Park, Noh-Yil Myung, Jae-Young Um, Seung-Heon Hong</p>
Excessive nitric oxide (NO) production is toxic to the cochlea and induces hearing loss. However, the mechanism through which NO induces ototoxicity has not been completely understood. The aim of this study was to gain further insight into the mechanism mediating NO-induced toxicity in auditory HEI-OC1 cells and in <i>ex vivo</i> analysis. We also elucidated whether and how epigallocatechin-3-gallate (EGCG), the main component of green tea polyphenols, regulates NO-induced auditory cell damage. To investigate NO-mediated ototoxicity, <i>S</i>-nitroso-<i>N</i>-acetylpenicillamine (SNAP) was used as an NO donor. SNAP was cytotoxic, generating reactive oxygen species, releasing cytochrome <i>c</i>, and activating caspase-3 in auditory cells. NO-induced ototoxicity also mediated the nuclear factor (NF)-κB/caspase-1 pathway. Furthermore, SNAP destroyed the orderly arrangement of the 3 outer rows of hair cells in the basal, middle, and apical turns of the organ of Corti from the cochlea of Sprague–Dawley rats at postnatal day 2. However, EGCG counteracted this ototoxicity by suppressing the activation of caspase-3/NF-κB and preventing the destruction of hair cell arrays in the organ of Corti. These findings may lead to the development of a model for pharmacological mechanism of EGCG and potential therapies against ototoxicity.Rosmarinic Acid, Active Component of Dansam-Eum Attenuates Ototoxicity of Cochlear Hair Cells through Blockage of Caspase-1 ActivityHyun-Ja JeongYoungjin ChoiMin-Ho KimIn-Cheol KangJeong-Han LeeChanny ParkRaekil ParkHyung-Min Kim10.1371/journal.pone.00188152011-04-15T14:00:00Z2011-04-15T14:00:00Z<p>by Hyun-Ja Jeong, Youngjin Choi, Min-Ho Kim, In-Cheol Kang, Jeong-Han Lee, Channy Park, Raekil Park, Hyung-Min Kim</p>
Cisplatin causes auditory impairment due to the apoptosis of auditory hair cells. There is no strategy to regulate ototoxicity by cisplatin thus far. Dansam-Eum (DSE) has been used for treating the central nerve system injury including hearing loss in Korea. However, disease-related scientific investigation by DSE has not been elucidated. Here, we demonstrated that DSE and its component rosmarinic acid (RA) were shown to inhibit apoptosis of the primary organ of Corti explants as well as the auditory cells. Administration of DSE and RA reduced the thresholds of the auditory brainstem response in cisplatin-injected mice. A molecular docking simulation and a kinetic assay show that RA controls the activity of caspase-1 by interaction with the active site of caspase-1. Pretreatment of RA inhibited caspase-1 downstream signal pathway, such as the activation of caspase-3 and 9, release of cytochrome <i>c</i>, translocation of apoptosis-inducing factor, up-regulation of Bax, down-regulation of Bcl-2, generation of reactive oxygen species, and activation of nuclear factor-κB. Anticancer activity by cisplatin was not affected by treatment with RA in SNU668, A549, HCT116, and HeLa cells but not B16F10 cells. These findings show that blocking a critical step by RA in apoptosis may be useful strategy to prevent harmful side effects of ototoxicity in patients with having to undergo chemotherapy.