Anti-alopecia mechanisms of soymetide-4, an immunostimulating peptide derived from soy beta-conglycinin.
Previously, we found that orally administered soymetide-4 (MITL), an immunostimulating peptide derived from soybean beta-conglycinin alpha' subunit, suppressed alopecia induced by the anti-cancer drug etoposide in neonatal rats. Soymetide-4 has weak affinity for N-formyl-methionyl-leucyl-phenylalanine (fMLP) receptor. fMLP showed an anti-alopecia effect after intraperitoneal administration, though it was inactive after oral administration. Anti-alopecia effect of fMLP was blocked by pyrilamine or cimetidine, antagonists for histamine H1 or H2 receptor, respectively. However, the anti-alopecia effect of soymetide-4 was not inhibited by the histamine antagonists but by indomethacin, an inhibitor of cyclooxygenase (COX), or AH-23848B, an antagonist of the EP4 receptor for PGE2. Anti-alopecia effect of soymetide-4 was also blocked by pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB (NF-kappaB). These results suggest that PGE2, which is produced after activation of COX by soymetide-4, might suppress apoptosis of hair matrix cells and etoposide-induced alopecia by activating NF-kappaB.
Tsuruki
Takahiro
T
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan.
Takahata
Kyoya
K
Yoshikawa
Masaaki
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000284:Administration, Oral; D000505:Alopecia / Q000517:prevention & control*; D000818:Animals; D052179:Antigens, Plant; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001713:Biphenyl Compounds / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000633:toxicity; D005260:Female; D005916:Globulins / Q000737:chemistry; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000187:drug effects; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D055314:Seed Storage Proteins; D030262:Soybean Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013859:Thiocarbamates / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D052179:Antigens, Plant; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D005916:Globulins; D006634:Histamine H1 Antagonists; D016328:NF-kappa B; D010446:Peptide Fragments; D011759:Pyrrolidines; D044042:Receptors, Formyl Peptide; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D055314:Seed Storage Proteins; D030262:Soybean Proteins; D013859:Thiocarbamates; C013894:beta-conglycinin protein, Glycine max; C494860:soymetide-4; C020972:pyrrolidine dithiocarbamic acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005047:Etoposide; C046926:AH 23848; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin