Proteomic analysis in NSAIDs-treated primary cardiomyocytes.
NSAIDs (non-steroidal anti-inflammatory drugs) are widely used for the treatment of a variety of inflammatory diseases, but many of them were withdrawn from the market due to their cardiovascular toxicity. In this study, we tried to identify proteins responding to the cellular toxicity in NSAIDs-treated primarily cultured cardiomyocytes using 2-D proteomic analysis. We used seven different NSAIDs (celecoxib, rofecoxib, valdecoxib, diclofenac, naproxen, ibuprofen, and meloxicam) possessing each different degree of cardiovascular risk. Overall protein spots were similar in all NSAIDs-treated cells although numbers of decreased proteins were about 2-fold higher in celecoxib or rofecoxib-treated cells than in cells incubated with other NSAIDs. Many stress-related proteins, cardiac muscle movement proteins and proteins involved in membrane organization have been isolated. Among them, Septin-8, a filament scaffolding protein, showed its specific expression pattern depending on the extent of drug toxicity. Its expression level was low in cells treated by relatively high toxic drugs such as celecoxib, diclofenac, valdecoxib, and rofecoxib. On the contrary, Septin-8 was similarly expressed in control cells in the presence of less toxic drugs such ibuprofen, naproxen, and meloxicam. This data suggests that Septin-8 differentially responds to each NSAID.
Department of Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, JinJu, Republic of Korea.
Seon Mi
SM
Baek
Jin Sook
JS
Ahn
Hae Sook
HS
Noh
Jaeyong
J
Park
Sang Soo
SS
Kang
Deok Ryong
DR
Kim
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000145:classification / Q000633:toxicity*; D015153:Blotting, Western; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D015180:Electrophoresis, Gel, Two-Dimensional; D019204:GTP-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D018570:Risk Assessment; D058112:Septins; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D019204:GTP-Binding Proteins; C539978:Septin8 protein, rat; D058112:Septins