Thimerosal-induced cytosolic Ca2+ elevation and subsequent cell death in human osteosarcoma cells

Chang, Hong‐Tai; Liu, Chung-Shin; Chou, Chiang-Ting; Hsieh, Ching-Hong; Chang, Chih-Hung; Chen, Wei‐Chuan; Liu, Shiuh–Inn; Hsu, Shu-Shong; Chen, Jin-Shyr; Jiann, Bang‐Ping; Jan, Chung‐Ren

doi:10.1016/j.phrs.2005.05.006

Cited by 10 publications

(4 citation statements)

References 25 publications

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“…8 However, an abnormal [Ca 2+ ] i rise is cytotoxic and can lead to apoptosis, dysfunction of proteins, interference of ion flux, etc. 9 Thimerosal has been shown to increase [Ca 2+ ] i in different cell types, including osteosarcoma cells, 10 rat cerebellar neurons, 11 salivary duct cells, 12 parathyroid cells, 13 hair cells, 14 etc.…”

Section: Introductionmentioning

confidence: 99%

Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells

et al. 2009

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The effect of thimerosal on cytosolic free Ca2+ concentrations ([Ca2+]i ) in human oral cancer cells (OC2) is unclear. This study explored whether thimerosal changed basal [Ca2+]i levels in suspended OC2 cells using fura-2. Thimerosal at concentrations between 1and 50 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca 2+. Thimerosal-induced Ca2+ influx was not blocked by L-type Ca2+ entry inhibitors and protein kinase C modulators (phorbol 12-myristate 13-acetate [PMA] and GF109203X). In Ca2+-free medium, 50 μM thimerosal failed to induce a [Ca2+]i rise after pretreatment with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with U73122 did not change thimerosal-induced [Ca2+]i rises. At concentrations between 5 and 10 μM, thimerosal killed cells in a concentration-dependent manner. The cytotoxic effect of 8 μM thimerosal was potentiated by prechelating cytosolic Ca2+ with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetate/acetomethyl (BAPTA/ AM). Flow cytometry data suggested that 1—7 μM thimerosal-induced apoptosis in a concentration-dependent manner. Collectively, in OC2 cells, thimerosal-induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx through non—L-type Ca2+ channels. Thimerosal killed cells in a concentration-dependent manner through apoptosis.

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Section: Introductionmentioning

confidence: 99%

Effect of thimerosal on Ca2+ movement and viability in human oral cancer cells

et al. 2009

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“…Currently, there is a semi-selective small molecule MBOAT7 inhibitor (thimerosal), (50) which has shown some promise as a potential as a cancer therapeutic (51)(52)(53). However, thimerosal likely has many enzymatic targets, and additional structure-activity-relationship (SAR) drug discovery efforts are needed to find more selective inhibitors.…”

Section: Discussionmentioning

confidence: 99%

MBOAT7-Driven Phosphatidylinositol Remodeling Promotes the Progression of Clear Cell Renal Carcinoma

Neumann

Zhang

Silver

et al. 2019

Preprint

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The most common kidney cancer, clear cell Renal Cell Carcinoma (ccRCC) is closely associated with obesity. In fact, the "clear cell" variant of RCC is given this name due to large lipid droplets within the tumor cells. Although it is well appreciated that renal lipid metabolism is altered in ccRCC, the mechanisms driving this are not well understood. Leveraging a shotgun lipidomics approach we have identified a lipid signature for ccRCC that includes an increase in arachidonic acid-enriched phosphatidylinositols (AA-PI). In parallel, we found that ccRCC tumors have increased expression of the acyltransferase enzyme membrane bound O-acyltransferase domain containing 7 (MBOAT7) that contributes to AA-PI synthesis. In ccRCC patients, MBOAT7 expression increases with tumor grade, and increased MBOAT7 expression correlates with poor survival. Genetic deletion of MBOAT7 in ccRCC cells decreases proliferation and induces cell cycle arrest, and MBOAT7 -/cells fail to form tumors in vivo. RNAseq of MBOAT7 -/cells identified alterations in cell migration and extracellular matrix organization, which were functionally validated in migration assays. Our work highlights the accumulation of AA-PI in ccRCC and demonstrate a novel way to decrease the AA-PI pool in ccRCC by limiting MBOAT7. Our data reveal that metastatic ccRCC is associated with altered AA-PI metabolism, and identify MBOAT7 as a novel target in advanced ccRCC.

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“…It can also affect human osteosarcoma cells by increasing the concentration-dependent amount of free calcium in the citosol. At concentrations of 5, 10 and 20 µM, thimerosal can cause the death of 33, 55 and 100% of cells, respectively (21). Different human neuroblastoma cell lines while treated with thimerosal show a decrease in cell viability, depending on the dose of the compound and the time of exposure.…”

Section: Discussionmentioning

confidence: 99%