{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:30:31Z","timestamp":1777667431262,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T00:00:00Z","timestamp":1619568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Kaohsiung Municipal United Hospital","award":["109-10"],"award-info":[{"award-number":["109-10"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:p>\n                    A lot of phenolic compounds are widespread in industrial effluents and they are considerable environmental pollutants. Being a compound commercially available, the effect of a bearing-wastewater phenolic compound 3,4-dimethylphenol (3,4-DMP) on Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis and its related physiology has not been explored in cultured human kidney cell models. The aim of this study was to explore the effect of 3,4-DMP on [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    and viability in HK-2 human proximal renal tubular epithelial cells. In terms of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling, 3,4-DMP (5\u2013100 \u03bcM) induced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    rises only in HK-2 cells and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    removal reduced the signal by 40%. In Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -containing medium, 3,4-DMP-induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry was inhibited by 20% by a modulator of store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels (2-APB), and by a PKC activator (PMA) and inhibitor (GF109203X). Moreover, 3,4-DMP-induced Mn\n                    <jats:sup>2+<\/jats:sup>\n                    influx suggesting of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry. In Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -free medium, inhibition of PLC with U73122 abolished 3,4-DMP-induced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    rises. Furthermore, treatment with the endoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pump inhibitor thapsigargin abolished 3,4-DMP-evoked [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    rises. Conversely, treatment with 3,4-DMP abolished thapsigargin-evoked [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    rises. Regarding to cell viability, 3,4-DMP (60\u2013140 \u03bcM) killed cells in a concentration-dependent fashion in HK-2 cells. Chelation of cytosolic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    with BAPTA-AM partially reversed cytotoxicity of 3,4-DMP. Collectively, our data suggest that in HK-2 cells, 3,4-DMP-induced [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    rises by evoking Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry via PKC-sensitive store-operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry and PLC-dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release from the endoplasmic reticulum. 3,4-DMP also caused cytotoxicity that was linked to preceding [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>i<\/jats:sub>\n                    rises. Our findings provide new insight into the cytotoxic effects of 3,4-DMP and the possible mechanisms underlying these effects.\n                  <\/jats:p>","DOI":"10.1177\/09603271211013453","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T03:13:25Z","timestamp":1619579605000},"page":"1899-1908","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of a bearing-wastewater phenolic compound (3,4-dimethylphenol, 3,4-DMP) treatment on Ca\n                    <sup>2+<\/sup>\n                    homeostasis and its related cytotoxicity in human proximal renal tubular epithelial cells"],"prefix":"10.1177","volume":"40","author":[{"given":"K-J","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Nephrology, Kaohsiung Municipal United Hospital, Kaohsiung"},{"name":"Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-6377","authenticated-orcid":false,"given":"W-Z","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan"},{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,4,28]]},"reference":[{"key":"bibr1-09603271211013453","doi-asserted-by":"publisher","DOI":"10.1016\/j.jenvman.2015.06.046"},{"key":"bibr2-09603271211013453","first-page":"20","volume":"77","author":"Srivastava S","year":"2015","journal-title":"J Environ 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