Hemorphins act as homeostatic agents in response to endotoxin-induced stress.
The effect of synthetic LVV-hemorphin-7 and hemorphin-7 on hypothalamo-pituitary-adrenocortical axis activity in response to endotoxin-induced stress was studied. The intraperitoneal (ip) endotoxin (lipopolysaccaride, LPS) (0.5 mg/kg) administration in combination with hemorphin (1 mg/kg) induce significant decrease in plasma corticosterone and modest decrease in plasma levels of tumor necrosis factor-alpha (TNFalpha) in compare with elevated levels of both corticosterone and TNFalpha in plasma of rats received LPS administration alone. Increased activity of calcineurin in both plasma and brain of rats received ip administration of LPS, was recovered under LPS + hemorphin treatment. In two independent proteome analysis, using 2-dimensional fluorescence difference gel electrophoresis and the isotope coded protein label technology, peptidyl-prolyl cis-trans-isomerase A (cyclophilin A) was identified as regulated by hemorphins protein in mouse brain. A therapeutic potential of hemorphins and mechanisms of their homeostatic action in response to endotoxin-induced stress are discussed.
Barkhudaryan
Nina
N
H. Buniatian Institute of Biochemistry of National Academy of Sciences, 5/1 P. Sevag Str, Yerevan, 0014, Republic of Armenia. nbarkh@sci.am
Zakaryan
Hermine
H
Sarukhanyan
Flora
F
Gabrielyan
Anna
A
Dosch
Dominik
D
Kellermann
Josef
J
Lottspeich
Friedrich
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D021984:Cyclophilin A / Q000096:biosynthesis; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D006706:Homeostasis; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D020104:Immunophilins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D006454:Hemoglobins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C085122:hemorphin 7; C074309:LVV-hemorphin-7; D019703:Calcineurin; D021984:Cyclophilin A; D020104:Immunophilins; D003345:Corticosterone