Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular cells

Human & Experimental Toxicology
S I LiuC R Jan

Abstract

The effect of melittin on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and viability is largely unknown. This study examined whether melittin alters Ca(2+) levels and causes Ca(2+)-dependent cell death in Madin-Darby canine kidney (MDCK) cells. [Ca(2+)](i) and cell death were measured using the fluorescent dyes fura-2 and WST-1 respectively. Melittin at concentrations above 0.5 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced by 75% by removing extracellular Ca(2+). The melittin-induced Ca(2+) influx was also implicated by melittin-caused Mn(2+) influx. After pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor), melittin-induced Ca(2+) release was inhibited; and conversely, melittin pretreatment abolished thapsigargin-induced Ca(2+) release. At concentrations of 0.5-20 microM, melittin killed cells in a concentration-dependent manner. The cytotoxic effect of 0.5 microM melittin was nearly completely reversed by prechelating cytosolic Ca(2+) with BAPTA. Melittin at 0.5-2 microM caused apoptosis as assessed by flow cytometry of propidium iodide staining. Collectively, in MDCK cells, melittin induced a [Ca(2+)](i) rise by causing Ca(2+) release...Continue Reading

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Citations

Jul 21, 2011·Drug and Chemical Toxicology·Chun-Chi KuoChung-Ren Jan
Nov 4, 2009·Journal of Receptor and Signal Transduction Research·Chun-Jen HuangChung-Ren Jan
Jan 21, 2015·The Kaohsiung Journal of Medical Sciences·Fang-Jin LiuChung-Ren Jan
Jun 19, 2010·Progress in Neurobiology·Jun Chen, William R Lariviere
Nov 10, 2012·Journal of Receptor and Signal Transduction Research·Chung-Pin LiuChung-Ren Jan
Sep 1, 2015·PLoS Computational Biology·Logan C BrooksRoni Rosenfeld
May 19, 2016·PLoS Computational Biology·Andrew F Neuwald, Stephen F Altschul
Dec 22, 2016·PLoS Computational Biology·Andrew F Neuwald, Stephen F Altschul
Sep 23, 2009·Human & Experimental Toxicology·Yi-Chien FangChung-Ren Jan
Sep 7, 2013·Clinical Journal of the American Society of Nephrology : CJASN·Ling ZhangPing Fu
Feb 1, 2015·Human & Experimental Toxicology·H-H ChengC-R Jan
Apr 25, 2013·Human & Experimental Toxicology·Y-C FangC-R Jan

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