Expression of apoptosis on rat liver by hepatic vagus hyperactivity after ventromedial hypothalamic lesioning.
We examined whether the Fas (APO-1/CD95)/Fas ligand system mediates apoptosis in rats with ventromedial hypothalamus (VMH) lesions. Northern and Western blotting indicated that VMH lesions lead to a significant increase in Fas mRNA and protein expression from day 1 to day 7 and in Fas ligand mRNA and protein expression from day 2 to day 7. Immunohistochemistry indicated that the region of strongest Fas expression shifted from acinar zone 1 to zones 2 and 3 by day 7 after VMH lesioning and that at days 2-7 Fas-ligand-positive hepatocyte cell membranes and cytoplasm were randomly distributed in acinar zones 1-3. We also analyzed activation of caspase 3-like proteases in hepatocytes, Kupffer cells, and sinusoidal endothelial cells. Spectrofluorometric assay demonstrated that caspase 3-like activity significantly increased only in hepatocytes after VMH lesioning. Moreover, electron microscopy and TUNEL assay showed that VMH lesions induced apoptosis. All of these effects were completely inhibited by hepatic vagotomy and administration of atropine. Vagal firing after VMH lesioning may stimulate Fas/Fas ligand system-mediated apoptosis through the cholinergic system in the rat liver.
Kiba
T
T
Third Department of Internal Medicine, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004. takkiba@earthlink.net
Saito
S
S
Numata
K
K
Kon
Y
Y
Mizutani
T
T
Sekihara
H
H
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001286:Atropine Derivatives / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000201:enzymology; D053222:Fas Ligand Protein; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology; D007728:Kupffer Cells / Q000166:cytology / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000294:innervation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014158:Transcription, Genetic; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*; D019014:fas Receptor / Q000032:analysis / Q000235:genetics
D001286:Atropine Derivatives; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor; C006649:methylatropine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases