{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:40:48Z","timestamp":1791247248009,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2003,1,9]],"date-time":"2003-01-09T00:00:00Z","timestamp":1042070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Matrix vesicles released by epiphyseal growth plate chondrocytes are known to contain a significant quantity of labile Zn<jats:sup>2+<\/jats:sup>. Zonal analysis of chicken metatarsal bones showed that the resting\/proliferative region of the growth plate contained high levels of Zn<jats:sup>2+<\/jats:sup> with significantly lower levels in the hypertrophic cartilage suggesting a loss of cellular Zn<jats:sup>2+<\/jats:sup> as the chondrocytes mature. Intracellular labile Zn<jats:sup>2+<\/jats:sup> was measured in primary cultures of growth plate chondrocytes by assay with the fluorescent Zn\u2010chelator toluenesulfonamidoquinoline (TSQ) and imaged by multi\u2010photon laser scanning microscopy (MPLSM) with the TSQ derivative zinquin. Short\u2010term exposure to Zn<jats:sup>2+<\/jats:sup>, both in the presence and absence of pyrithione resulted in significant increases in cytosolic Zn<jats:sup>2+<\/jats:sup>. Treatment with the membrane\u2010permeant Zn<jats:sup>2+<\/jats:sup> chelator TPEN rapidly reduced the levels of labile Zn<jats:sup>2+<\/jats:sup> and triggered apoptosis. Cytosolic Zn<jats:sup>2+<\/jats:sup> levels were significantly reduced following 24\u2010h incubations with known inducers of chondrocyte apoptosis. The loss of intracellular Zn<jats:sup>2+<\/jats:sup> was accompanied by a significant reduction in the cytosolic metal\u2010binding protein metallothionein. Examination of Zn<jats:sup>2+<\/jats:sup>\u2010treated cells with MPLSM showed uniformly higher zinquin fluorescence. Treatment of Zn<jats:sup>2+<\/jats:sup>\u2010loaded cells with TPEN quenched zinquin fluorescence confirming that the observed fluorescence in chondrocytes is due to the presence of intracellular Zn<jats:sup>2+<\/jats:sup>. A dose\u2010dependent increase in zinquin fluorescence was observed in cells treated with a range of Zn<jats:sup>2+<\/jats:sup> concentrations. Short\u2010term treatment of cultured chondrocytes with apoptosis\u2010inducing chemicals resulted in transient increases in intracellular labile Zn<jats:sup>2+<\/jats:sup>. These results indicate that Zn<jats:sup>2+<\/jats:sup> is mobilized from intracellular binding sites in the early stages of chondrocyte apoptosis and is subsequently lost from the cells. The early mobilization of Zn<jats:sup>2+<\/jats:sup> provides a mechanism for its movement to matrix vesicles and the extracellular matrix. J. Cell. Biochem. 88: 954\u2013969, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.10446","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T23:10:35Z","timestamp":1048029035000},"page":"954-969","source":"Crossref","is-referenced-by-count":20,"title":["Intracellular zinc fluxes associated with apoptosis in growth plate chondrocytes"],"prefix":"10.1002","volume":"88","author":[{"given":"Glenn R.","family":"Sauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Della M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Cahalane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia N.Y.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy E.","family":"Wuthier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,2,26]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041630109"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.1.205"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.41.1.59"},{"key":"e_1_2_6_5_1","first-page":"213","article-title":"The influence of trace elements on the skeleton","volume":"27","author":"Asling CW","year":"1963","journal-title":"Clin Orthop"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.6.2473"},{"key":"e_1_2_6_7_1","first-page":"230","volume-title":"Protein methods","author":"Bollag DM","year":"1991"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.4.1941"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.10.070190.000431"},{"key":"e_1_2_6_10_1","first-page":"143","article-title":"Histochemical localization of calcium in growth plate mitochondria and matrix vesicles","volume":"35","author":"Brighton CT","year":"1976","journal-title":"Fed Proc"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.1999.00825.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00624-4"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1985.65.2.238"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(91)05089-E"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711230404"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092190303"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(92)90384-9"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(87)90042-2"},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"18580","DOI":"10.1016\/S0021-9258(18)55102-4","article-title":"Identification, purification, and characterization of a calcium\u2010dependent endonuclease (NUC18) from apoptotic rat thymocytes","volume":"266","author":"Gaido ML","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030409"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca2+ indicators with greatly improved fluorescence properties","volume":"260","author":"Grynkiewicz G","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_6_22_1","first-page":"443","volume-title":"Biological mineralization","author":"Guggenheim K","year":"1972"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(90)86093-B"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199809)41:9<1632::AID-ART14>3.0.CO;2-A"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3094"},{"key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1002\/jbmr.5650101216","article-title":"End labeling studies of fragmented DNA in the avian growth plate: Evidence of apoptosis in terminally differentiated chondrocytes","volume":"12","author":"Hatori M","year":"1995","journal-title":"J Bone Min Res"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7991"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950170709"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)90024-5"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070280606"},{"key":"e_1_2_6_31_1","first-page":"45","article-title":"Are matrix vesicles apoptotic bodies?","volume":"101","author":"Kardos TB","year":"1982","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199907)42:7<1528::AID-ANR28>3.0.CO;2-9"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.13.7557017"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1564"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.35.040195.003223"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002239900442"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.5.1500S"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02441159"},{"key":"e_1_2_6_39_1","first-page":"101","article-title":"Chelator of intracellular zinc triggers apoptosis in mouse thymocytes","volume":"69","author":"McCabe M","year":"1993","journal-title":"Lab Invest"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx950109y"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/joca.2000.0380"},{"key":"e_1_2_6_42_1","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1002\/j.1460-2075.1996.tb00527.x","article-title":"ZnT\u20102, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration","volume":"15","author":"Palmiter RD","year":"1996","journal-title":"EMBO J"},{"key":"e_1_2_6_43_1","first-page":"2805","article-title":"Zinc uptake and metabolism by hepatocytes","volume":"45","author":"Pattison SE","year":"1986","journal-title":"Fed Proc"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.30.18530"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)70782-3"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1997.12.5.795"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.1178"},{"key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1093\/jn\/131.4.1142","article-title":"Reduced growth and skeletal changes in zinc\u2010deficient growing rats are due to impaired growth plate activity and inanition","volume":"131","author":"Rossi L","year":"2000","journal-title":"J Nutr"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-6009(89)90080-9"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19980101)68:1<110::AID-JCB11>3.0.CO;2-L"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-24-09554.1997"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7112108"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(77)90080-X"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00439.2001"},{"key":"e_1_2_6_55_1","first-page":"134","article-title":"The influence of zinc on apoptosis","volume":"25","author":"Sunderman FW","year":"1995","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.5.1459S"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1993.73.1.79"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.4.665"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400218"},{"key":"e_1_2_6_60_1","doi-asserted-by":"crossref","first-page":"21346","DOI":"10.1016\/S0021-9258(19)30086-9","article-title":"Induction of mineral deposition by primary cultures of chicken growth plate chondrocytes in ascorbate\u2010containing media","volume":"264","author":"Wu LY","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_6_61_1","doi-asserted-by":"crossref","first-page":"25084","DOI":"10.1016\/S0021-9258(19)74574-8","article-title":"Characterization of the nucleational core complex responsible for mineral induction by growth plate cartilage matrix","volume":"268","author":"Wu LNY","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240570206"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(75)90087-9"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02012777"},{"key":"e_1_2_6_65_1","first-page":"231","article-title":"Mechanism of matrix vesicle\u2010mediated mineralization of cartilage","volume":"1","author":"Wuthier RE","year":"1988","journal-title":"ISI Atlas Sci: Biochem"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/123.suppl_2.301"},{"key":"e_1_2_6_67_1","first-page":"1093","article-title":"Physiological role for zinc in prevention of apoptosis gene\u2010directed death","volume":"24","author":"Zalewski PD","year":"1991","journal-title":"Biochem Int"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2960403"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-5521(94)90005-1"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199612)180:4<430::AID-PATH691>3.0.CO;2-H"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.10446","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.10446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T14:43:52Z","timestamp":1700232232000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.10446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2,26]]},"references-count":69,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2003,4]]}},"alternative-id":["10.1002\/jcb.10446"],"URL":"https:\/\/doi.org\/10.1002\/jcb.10446","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,2,26]]}}}