{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T23:44:00Z","timestamp":1777851840839,"version":"3.51.4"},"reference-count":22,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T00:00:00Z","timestamp":1157068800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Histochem Cytochem."],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:p>\n                    Tripeptidyl peptidase I (TPP-I) is a lysosomal peptidase with unclear physiological function. TPP-I deficiency is associated with late-infantile neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative disease of childhood that is characterized by loss of neurons and photoreceptor cells. We have developed two novel fluorogenic substrates, [Ala-Ala-Phe]\n                    <jats:sub>2<\/jats:sub>\n                    -rhodamine 110 and [Arg-Nle-Nle]\n                    <jats:sub>2<\/jats:sub>\n                    -rhodamine 110, that are cleaved by TPP-I in living cells. Fluorescence of liberated rhodamine 110 was detected by flow cytometry and was dependent on the level of TPP-I expression. Rhodamine-related fluorescence could be suppressed by preincubation with a specific inhibitor of TPP-I. When investigated by fluorescent confocal microscopy, rhodamine signals colocalized with lysosomal markers. Thus, cleavage of these rhodamide-derived substrates is a marker for mature enzymatically active TPP-I. In addition, TPP-I-induced cleavage of [Ala-Ala-Phe]\n                    <jats:sub>2<\/jats:sub>\n                    -rhodamine 110 could be visualized in primary neurons. We conclude that [Ala-Ala-Phe]\n                    <jats:sub>2<\/jats:sub>\n                    -rhodamine 110 and [Arg-Nle-Nle]\n                    <jats:sup>2<\/jats:sup>\n                    -rhodamine 110 are specific substrates for determining TPP-I activity and intracellular localization in living cells. Further, these substrates could be a valuable tool for studying the neuronal pathology underlying classical late-infantile NCL. This article contains online supplemental material at http:\/\/www.jhc.org . Please visit this article online to view these materials.\n                  <\/jats:p>","DOI":"10.1369\/jhc.5a6900.2006","type":"journal-article","created":{"date-parts":[[2006,6,16]],"date-time":"2006-06-16T21:17:31Z","timestamp":1150492651000},"page":"991-996","source":"Crossref","is-referenced-by-count":3,"title":["Detection of Tripeptidyl Peptidase I Activity in Living Cells by Fluorogenic Substrates"],"prefix":"10.1177","volume":"54","author":[{"given":"Robert","family":"Steinfeld","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology, University of G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens C.","family":"Fuhrmann","sequence":"additional","affiliation":[{"name":"Centre for Molecular Neurobiology, University of Hamburg, Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jutta","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology, University of G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2006,9,1]]},"reference":[{"key":"bibr1-jhc.5A6900.2006","first-page":"565","volume":"50","author":"Dikov A","year":"2004","journal-title":"Cell Mol Biol"},{"key":"bibr2-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2207"},{"key":"bibr3-jhc.5A6900.2006","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.1523\/JNEUROSCI.22-13-05393.2002","volume":"22","author":"Fuhrmann JC","year":"2002","journal-title":"J Neurosci"},{"key":"bibr4-jhc.5A6900.2006","first-page":"3877","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Hofmann SL","year":"2001"},{"key":"bibr5-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1021\/bi9913395"},{"key":"bibr6-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600576"},{"key":"bibr7-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61734-3"},{"key":"bibr8-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1038\/ni1090"},{"key":"bibr9-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.140.6.1331"},{"key":"bibr10-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1042\/bj2090299"},{"key":"bibr11-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008562200"},{"key":"bibr12-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvi110"},{"key":"bibr13-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(04)00074-3"},{"key":"bibr14-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5333.1802"},{"key":"bibr15-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2729-04.2004"},{"key":"bibr16-jhc.5A6900.2006","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1093\/clinchem\/46.7.1005","volume":"46","author":"Sohar I","year":"2000","journal-title":"Clin Chem"},{"key":"bibr17-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh264"},{"key":"bibr18-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507336200"},{"key":"bibr19-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(98)00012-0"},{"key":"bibr20-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005665732189"},{"key":"bibr21-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1007\/BF00966768"},{"key":"bibr22-jhc.5A6900.2006","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6807-3-8"}],"container-title":["Journal of Histochemistry &amp; Cytochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1369\/jhc.5A6900.2006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1369\/jhc.5A6900.2006","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1369\/jhc.5A6900.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:26:55Z","timestamp":1777501615000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1369\/jhc.5A6900.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1369\/jhc.5A6900.2006"],"URL":"https:\/\/doi.org\/10.1369\/jhc.5a6900.2006","relation":{},"ISSN":["0022-1554","1551-5044"],"issn-type":[{"value":"0022-1554","type":"print"},{"value":"1551-5044","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9]]}}}