title: Identification of proteasome subunit beta type 6 (PSMB6) associated with deltamethrin resistance in mosquitoes by proteomic and bioassay analyses.
abstract: Deltamethrin (DM) insecticides are currently being promoted worldwide for mosquito control, because of the high efficacy, low mammalian toxicity and less environmental impact. Widespread and improper use of insecticides induced resistance, which has become a major obstacle for the insect-borne disease management. Resistance development is a complex and dynamic process involving many genes. To better understand the possible molecular mechanisms involved in DM resistance, a proteomic approach was employed for screening of differentially expressed proteins in DM-susceptible and -resistant mosquito cells. Twenty-seven differentially expressed proteins were identified by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). Four members of the ubiquitin-proteasome system were significantly elevated in DM-resistant cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM resistance. Proteasome subunit beta type 6 (PSMB6) is a member of 20S proteasomal subunit family, which forms the proteolytic core of 26S proteasome. We used pharmaceutical inhibitor and molecular approaches to study the contributions of PSMB6 in DM resistance: the proteasome inhibitor MG-132 and bortezomib were used to suppress the proteasomal activity and siRNA was designed to block the function of PSMB6. The results revealed that both MG-132 and bortezomib increased the susceptibility in DM-resistant cells and resistance larvae. Moreover, PSMB6 knockdown decreased cellular viability under DM treatment. Taken together, our study indicated that PSMB6 is associated with DM resistance in mosquitoes and that proteasome inhibitors such as MG-132 or bortezomib are suitable for use as a DM synergist for vector control.
authors.affiliation: Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
authors.forename: Linchun
authors.initials: L
authors.lastname: Sun
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ye
authors.forename: Haibo
authors.initials: H
authors.lastname: Sun
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Donghui
authors.initials: D
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Changliang
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D009033:Culicidae / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000187:drug effects*; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D011719:Pyrazines / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; D019476:Insect Proteins; D007306:Insecticides; D007976:Leupeptins; D009570:Nitriles; D011719:Pyrazines; D011722:Pyrethrins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C017180:decamethrin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde