Upregulation of geranylgeranyltransferase I in bronchial smooth muscle of mouse experimental asthma: its inhibition by lovastatin.
RhoA has been recognized as an important protein for bronchial smooth muscle (BSM) contraction and hyperresponsiveness, and its activation is also regulated by geranylgeranyltransferase I (GGTase I). In the present study, the effects of repeated antigen exposure on the expression of GGTase I were determined in mouse BSMs. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen. Animals were also treated with lovastatin (4 mg/kg/day, i.p.) once a day prior to and during the antigen inhalation period. Western blot analyses revealed that GGTase I was upregulated in BSMs of the antigen-challenged mice. The systemic treatment with lovastatin attenuated the upregulation of GGTase I induced by antigen exposure. Interestingly, lovastatin also significantly reduced the protein expression of GGTase I in BSMs of control animals. We thus concluded that an upregulation of GGTase I in BSM might be, at least in part, involved in the development of antigen-induced airway hyperresponsiveness. Lovastatin might have therapeutic potential to ameliorate airway hyperresponsiveness in allergic bronchial asthma.
Chiba
Yoshihiko
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Japan. chiba@hoshi.ac.jp
Sato
Shunsuke
S
Misawa
Miwa
M
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology*; D001980:Bronchi / Q000201:enzymology*; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008148:Lovastatin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000201:enzymology*; D015854:Up-Regulation
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I