Functional alteration of guanine nucleotide binding proteins (Gs and Gi) in psoriatic epidermis.
Psoriatic involved epidermis has been characterized by a defective beta-adrenergic adenylate cyclase response. It is also characterized by increased cholera toxin- and forskolin-induced cyclic AMP accumulations. Due to the fact that receptor signals are transduced to adenylate cyclase through guanine nucleotides binding proteins (G-proteins), that affect cholera toxin- and forskolin-induced cyclic AMP accumulations, possible alterations of G-proteins of psoriatic involved and perilesional uninvolved epidermis by using toxin-catalyzed ADP-ribosylation and immunoblot analyses was investigated. Cholera toxin catalyzes ADP-ribosylation of stimulatory guanine nucleotides binding protein (Gs) in either trimeric (inactive) or monomeric (active) form, while islet activating protein (IAP) catalyzes ADP ribosylation of inhibitory guanine nucleotide binding protein (Gi) in only trimeric (inactive) form. Results indicate that although the psoriatic involved epidermis shows increased cholera toxin- and IAP-catalyzed ADP-ribosylations, the amounts of immunoreactive Gs alpha or Gi alpha are not significantly altered. The increase in IAP-catalyzed ADP-ribosylation indicates increased inactive Gi, explaining the increased forskolin-induced cyclic AMP accumulation. The increase in cholera toxin-catalyzed ADP-ribosylation of Gs explains the increased cholera toxin-induced cyclic AMP accumulation in the psoriatic involved epidermis.
Tamura
T
T
Department of Dermatology, Asahikawa Medical College, Japan.
Takahashi
H
H
Ishida-Yamamoto
A
A
Hashimoto
Y
Y
Iizuka
H
H
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000328:Adult; D000368:Aged; D002772:Cholera Toxin / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D037342:Pertussis Toxin; D011565:Psoriasis / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins