{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:09:46Z","timestamp":1760645386247,"version":"3.37.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":9923,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1988,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Glutamine synthetase shows a striking heterogeneous distribution in normal rat liver as consistently revealed by immunohistochemistry using a specific antiserum against the rat liver enzyme or a cross-reacting antiserum. The effects of zonal liver injury induced by allylformate or CC1<jats:sub>4<\/jats:sub> on this distribution and on the activity of glutamine synthetase as well as of enzymes with different acinar distribution were investigated. Treatment with allylformate or CC1<jats:sub>4<\/jats:sub> at appropriate concentrations led to severe hepatocyte necrosis in the periportal and perivenous zone, respectively, as revealed by histological examination and by the levels of serum marker enzymes. Exposure to allylformate (50 to 100 \u03bcl per kg) for less than 1 day did not change the distribution and activity of glutamine synthetase but reduced the specific activities of the urea cycle enzymes. In contrast, treatment with CC1<jats:sub>4<\/jats:sub> (1,000 \u03bcl per kg) strongly reduced the activity and the acinar region covered by glutamine synthetase but not, for instance, the activities of the urea cycle enzymes. These results in conjunction with the data obtained for other enzymes indicate that a short exposure to these hepatotoxins affects different enzyme activities in close accord with their preferential acinar localization. During prolonged exposure this initial response was often modified due to adaptation. In the case of glutamine synthetase, however, no adaptive appearance of glutamine synthetase in other parts of the acinus could be detected even if the cell population originally expressing this phenotype was destroyed. This extremely inflexible distribution suggests that glutamine synthetase expression is a matter of cell differentiation rather than of modulation by nutritional and hormonal factors (or their acinar gradients) as found for many other hepatic enzymes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840080421","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T21:24:46Z","timestamp":1172957086000},"page":"822-830","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":52,"title":["Alterations of hepatic enzyme levels and of the acinar distribution of glutamine synthetase in response to experimental liver injury in the rat"],"prefix":"10.1097","volume":"8","author":[{"given":"Rolf","family":"Gebhardt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-J\u00f6rg","family":"Burger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Heini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl-Ludwig","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dieter","family":"Mecke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840080421-BIB1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0005-8165(76)80083-2","volume":"157","author":"Rappaport","year":"1976","journal-title":"Beitr Path Bd"},{"key":"10.1002\/hep.1840080421-BIB2","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0968-0004(78)91764-4","volume":"3","author":"Jungermann","year":"1978","journal-title":"Trends Biochem Sci"},{"key":"10.1002\/hep.1840080421-BIB3","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/0016-5085(81)90732-0","volume":"80","author":"Gumucio","year":"1981","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840080421-BIB4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/hep.1840020316","volume":"2","author":"Jungemann","year":"1982","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840080421-BIB5","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/978-1-4684-5041-5_9","volume-title":"Regulation of hepatic metabolism. Intra- and intercellular compartmentation","author":"Jungermann","year":"1986","unstructured":". Metabolism of carbohydrates. In: , , eds. Regulation of hepatic metabolism. Intra- and intercellular compartmentation. New York: Plenum Press, 1986: 211\u2013244."},{"key":"10.1002\/hep.1840080421-BIB6","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/BF00507698","volume":"45","author":"Sasse","year":"1975","journal-title":"Histochemistry"},{"key":"10.1002\/hep.1840080421-BIB7","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1515\/bchm2.1976.357.2.1793","volume":"357","author":"Guder","year":"1976","journal-title":"Hoppe-Seyler's Z Physiol Chem"},{"key":"10.1002\/hep.1840080421-BIB8","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1515\/bchm3.1985.366.1.493","volume":"366","author":"Miethke","year":"1985","journal-title":"Biol Chem Hoppe Seyler"},{"key":"10.1002\/hep.1840080421-BIB9","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1515\/bchm2.1978.359.2.1561","volume":"359","author":"Brinkmann","year":"1978","journal-title":"Hoppe-Seyler's Z Physiol Chem"},{"key":"10.1002\/hep.1840080421-BIB10","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1515\/bchm3.1985.366.2.713","volume":"366","author":"Wittig","year":"1985","journal-title":"Biol Chem Hoppe Seyler"},{"key":"10.1002\/hep.1840080421-BIB11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF00279884","volume":"18","author":"Sasse","year":"1969","journal-title":"Histochemie"},{"key":"10.1002\/hep.1840080421-BIB12","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/978-1-4684-5041-5_16","volume-title":"Regulation of hepatic metabolism. 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New York: Plenum Press, 1986: 445\u2013469."},{"key":"10.1002\/hep.1840080421-BIB13","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/j.1460-2075.1983.tb01464.x","volume":"2","author":"Gebhardt","year":"1983","journal-title":"EMBO J"},{"key":"10.1002\/hep.1840080421-BIB14","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1177\/33.12.4067274","volume":"33","author":"Gaasbeek Janzen","year":"1985","journal-title":"J Histochem Cytochem"},{"key":"10.1002\/hep.1840080421-BIB15","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2220\/biomedres.4.235","volume":"4","author":"Saheki","year":"1983","journal-title":"Biomed Res"},{"key":"10.1002\/hep.1840080421-BIB16","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/35.1.2878950","volume":"35","author":"Gaasbeek Janzen","year":"1986","journal-title":"J Histochem Cytochem"},{"key":"10.1002\/hep.1840080421-BIB17","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/978-3-642-69754-8_7","volume-title":"Glutamate metabolism in mammalian tissues","author":"Gebhardt","year":"1984","unstructured":". 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