{"doi":"10.1016/j.pestbp.2019.03.015","title":"Uncovering malathion (an organophosphate insecticide) action on Ca2+ signal transduction and investigating the effects of BAPTA-AM (a cell-permeant Ca2+ chelator) on protective responses in glial cells","abstract":null,"journal":"Pesticide Biochemistry and Physiology","year":2019,"id":636649,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1652549,"name":"Chung-Ren Jan","orcid":null,"position":1,"is_corresponding":false},{"id":1652552,"name":"Wei-Zhe Liang","orcid":null,"position":2,"is_corresponding":false},{"id":1652544,"name":"Shu-Shong Hsu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Uncovering malathion (an organophosphate insecticide) action on Ca2+ signal transduction and investigating the effects of BAPTA-AM (a cell-permeant Ca2+ chelator) on protective responses in glial cells","abstract":"Malathion, one of commonly used organophosphate insecticides, has a wide range of toxic actions in different models. However, the effect of this compound on Ca<sup>2+</sup> homeostasis and its related cytotoxicity in glial cells is elusive. This study examined whether malathion evoked intracellular Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) rises and established the relationship between Ca<sup>2+</sup> signaling and cytotoxicity in normal human astrocytes, rat astrocytes and human glioblastoma cells. The data show that malathion induced concentration-dependent [Ca<sup>2+</sup>]<sub>i</sub> rises in Gibco<sup>®</sup> Human Astrocytes (GHA cells), but not in DI TNC1 normal rat astrocytes and DBTRG-05MG human glioblastoma cells. In GHA cells, this Ca<sup>2+</sup> signal response was reduced by removing extracellular Ca<sup>2+</sup>. In Ca<sup>2+</sup>-free medium, pretreatment with the endoplasmic reticulum Ca<sup>2+</sup> pump inhibitor thapsigargin abolished malathion-induced [Ca<sup>2+</sup>]<sub>i</sub> rises. Conversely, incubation with malathion abolished thapsigargin-induced [Ca<sup>2+</sup>]<sub>i</sub> rises. Inhibition of phospholipase C (PLC) with U73122 also blocked malathion-induced [Ca<sup>2+</sup>]<sub>i</sub> rises. In Ca<sup>2+</sup>-containing medium, malathion-induced [Ca<sup>2+</sup>]<sub>i</sub> rises was inhibited by store-operated Ca<sup>2+</sup> channel blockers (2-APB, econazole or SKF96365) and the protein kinase C (PKC) inhibitor GF109203X. Malathion (5-25 μM) concentration-dependently caused cytotoxicity in GHA, DI TNC1 and DBTRG-05MG cells. This cytotoxic effect was partially prevented by prechelating cytosolic Ca<sup>2+</sup> with BAPTA-AM (a selective Ca<sup>2+</sup> chelator) only in GHA cells. Together, in GHA but not in DI TNC1 and DBTRG-05MG cells, malathion induced [Ca<sup>2+</sup>]<sub>i</sub> rises by inducing PLC-dependent Ca<sup>2+</sup> release from the endoplasmic reticulum and Ca<sup>2+</sup> entry via PKC-sensitive store-operated Ca<sup>2+</sup> channels. Furthermore, malathion induced Ca<sup>2+</sup>-associated cytotoxicity, suggesting that Ca<sup>2+</sup> chelating may have a protective effect on malathion-induced cytotoxicity in normal human astrocytes.","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31153463","pmcid":null,"openalex_id":"https://openalex.org/W2928671422","authors":[],"funders":[{"funder_name":"Kaohsiung Veterans General Hospital","grant_id":"VGHKS108-115","title":null}],"total_grants":1,"fwci":1.3393,"citation_percentile":0.84615311,"influential_citations":0,"citation_trend":[{"year":2020,"count":3},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0048357519301002?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0048357519301002?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.pestbp.2019.03.015","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31153463","host_type":"repository"}],"fields_of_study":["Pesticide Exposure and Toxicity","Neuroscience and Neuropharmacology Research","Cholinesterase and Neurodegenerative Diseases"],"mesh_terms":["Animals","Calcium","Cell Line","Cell Survival","Chelating Agents","Endoplasmic Reticulum","Humans","Malathion","Neuroglia","Calcium Signaling","Rats"],"keywords":["Thapsigargin","BAPTA","Malathion","Endoplasmic reticulum","Phospholipase C","Protein kinase C","Organophosphate","Cytotoxicity","Fura-2","Intracellular","Biology","Chemistry","Calphostin C","Cell biology","Biochemistry","Molecular biology","Signal transduction","Cytosol","Enzyme","In vitro","glial cell","Ca(2+) Signaling","Bapta-am"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T17:26:37.945528Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}