Altered expression of neprilysin family members in the pituitary gland of sleep-disturbed rats, an animal model of severe fatigue.
Alterations of the expression of some peptidases in the pituitary gland of a fatigued rat model were identified. Rats were kept in a cage filled with water to a height of 1.5 cm to disturb deep sleep. After 24-h sleep disturbance, expression of neutral endopeptidase 24.11 (neprilysin) mRNA was increased in the intermediate lobe of the pituitary gland, whereas the mRNA expression of another family member, damage-induced neuronal endopeptidase, which is normally expressed in a subgroup of anterior pituitary cells, was significantly suppressed. These alterations were demonstrated by RT-PCR, northern blotting and in situ hybridization. Other family members, such as neprilysin 2 and endothelin converting enzyme-1, did not show any change in mRNA expression. An increase of neprilysin mRNA expression was not seen in any other tissues of the sleep-disturbed rats. The enzymatic activity of neprilysin was also increased in the pituitary. The augmentation of neprilysin expression and activity was prolonged as long as the sleep disturbance continued (up to 5 days), and returned to the basal level when rats were allowed to sleep freely. These results suggest that peptide processing and degradation in the pituitary may be an influential factor in fatigued states such as sleep disturbance.
Ogawa
Tokiko
T
Department of Anatomy and Neurobiology, Graduate School of Medicine, Osaka City University, Asahimachi, Osaka, Japan.
Kiryu-Seo
Sumiko
S
Tanaka
Masaaki
M
Konishi
Hiroyuki
H
Iwata
Nobuhisa
N
Saido
Takaomi
T
Watanabe
Yasuyoshi
Y
Kiyama
Hiroshi
H
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D004195:Disease Models, Animal; D005221:Fatigue / Q000209:etiology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D019004:Galanin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D013006:Growth Hormone / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D009418:S100 Proteins / Q000378:metabolism; D012893:Sleep Wake Disorders / Q000150:complications / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D009418:S100 Proteins; D019004:Galanin; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D013972:Thyrotropin; D013006:Growth Hormone; C492358:Ecel1 protein, rat; D008666:Metalloendopeptidases; D015260:Neprilysin