Mammalian thioredoxin reductase alters cytolytic activity of an antibacterial peptide.
Granulysin is a disulfide rich 9 kDa human tumoricidal protein produced by cytolytic cells. Here we show that thioredoxin reductase (TrxR) reduced a 23-residue peptide from granulysin (GranF2), and this markedly enhanced the killing of small cell lung cancer cells (SCLC) by GranF2. Cells treated with reduced GranF2 showed rapid ATP deletion within 90 min and strong annexin V staining after 4 h incubation. SCLC with elevated TrxR levels was more sensitive to oxidized GranF2 than normal cells. The levels of TrxR are enhanced in many cancer cells, including SCLC, and it is possible that cytolytic activity of cytolytic cells on SCLC may in part be mediated by granulysin and modulated by TrxR.
Björkhem-Bergman
Linda
L
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, S-14186 Stockholm, Sweden.
Jönsson-Videsäter
Kerstin
K
Paul
Christer
C
Björnstedt
Mikael
M
Andersson
Mats
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000737:chemistry / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism; D013997:Time Factors; D023084:alpha-Defensins / Q000378:metabolism
D017304:Annexin A5; D000900:Anti-Bacterial Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D004220:Disulfides; C075005:GNLY protein, human; D010455:Peptides; D011506:Proteins; D023084:alpha-Defensins; C094880:protegrin-1; D013879:Thioredoxins; D000255:Adenosine Triphosphate; D013880:Thioredoxin-Disulfide Reductase