title: L-cystathionine inhibits the mitochondria-mediated macrophage apoptosis induced by oxidized low density lipoprotein.
abstract: This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. zhumingzhu1988521@126.com.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. tangchaoshu@263.net.cn.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. 15201286434@163.com.
authors.forename: Siyao
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden. angie.dongliu@gmail.com.
authors.forename: Angie Dong
authors.initials: AD
authors.lastname: Liu
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping 58183, Sweden. lucas.holmberg20@gmail.com.
authors.forename: Lukas
authors.initials: L
authors.lastname: Holmberg
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. chenyh3094@sina.com.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. chunyu5781@163.com.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China. tangchaoshu@263.net.cn.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. jinhongfang51@126.com.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D003540:Cystathionine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D013481:Superoxides; D003540:Cystathionine; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9