{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:57:51Z","timestamp":1792677471257,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,11,24]]},"abstract":"<jats:p>\n                    Protein synthesis (PS) has been considered essential to sustain mammalian life, yet was found to be virtually arrested for weeks in brain and other organs of the hibernating ground squirrel,\n                    <jats:italic>Spermophilus tridecemlineatus<\/jats:italic>\n                    . PS,\n                    <jats:italic>in vivo<\/jats:italic>\n                    , was below the limit of autoradiographic detection in brain sections and, in brain extracts, was determined to be 0.04% of the average rate from active squirrels. Further, it was reduced 3-fold in cell-free extracts from hibernating brain at 37\u00b0C, eliminating hypothermia as the only cause for protein synthesis inhibition (active, 0.47 \u00b1 0.08 pmol\/mg protein per min; hibernator, 0.16 \u00b1 0.05 pmol\/mg protein per min,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). PS suppression involved blocks of initiation and elongation, and its onset coincided with the early transition phase into hibernation. An increased monosome peak with moderate ribosomal disaggregation in polysome profiles and the greatly increased phosphorylation of eIF2\u03b1 are both consistent with an initiation block in hibernators. The elongation block was demonstrated by a 3-fold increase in ribosomal mean transit times in cell-free extracts from hibernators (active, 2.4 \u00b1 0.7 min; hibernator, 7.1 \u00b1 1.4 min,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). No abnormalities of ribosomal function or mRNA levels were detected. These findings implicate suppression of PS as a component of the regulated shutdown of cellular function that permits hibernating ground squirrels to tolerate \u201ctrickle\u201d blood flow and reduced substrate and oxygen availability. Further study of the factors that control these phenomena may lead to identification of the molecular mechanisms that regulate this state.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.24.14511","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"14511-14516","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":280,"title":["Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation"],"prefix":"10.1073","volume":"95","author":[{"given":"Kai U.","family":"Frerichs","sequence":"first","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn B.","family":"Smith","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brenner","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"DeGracia","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Krause","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Marrone","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Dever","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Hallenbeck","sequence":"additional","affiliation":[{"name":"Stroke Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Cerebral Metabolism, National Institute of Mental Health, Biochemistry Section, Surgical Neurology Branch, National Institute of Neurologic Disorders and Stroke, and Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and Department of Emergency Medicine, Wayne State University, Detroit, MI 48201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,11,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1994.26"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.12.6.723"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199802000-00007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9493"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0305-0491(95)02043-8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00367312"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/416717"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(89)90007-5"},{"key":"e_1_3_3_9_2","first-page":"1","volume-title":"Advances in Comparative Environmental Physiology","author":"Wang L C H","year":"1988","unstructured":"L C H Wang Advances in Comparative Environmental Physiology, ed R Gilles (Springer, Berlin), pp. 1\u201345 (1988)."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)63265-3"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1992.60"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00965848"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.9341"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(83)90022-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00966123"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1976.tb01546.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199712000-00004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47829-5"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.8.4164"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90193-G"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(70)90091-4"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86634-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3498987"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0011-2240(92)90071-9"},{"key":"e_1_3_3_25_2","first-page":"927","volume":"80","author":"Derij L","year":"1985","unstructured":"L Derij, M B Shtark Comp Biochem Physiol 80B, 927\u2013934 (1985).","journal-title":"Comp Biochem Physiol"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.1.19"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)40638-7"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.56.2.291-315.1992"},{"key":"e_1_3_3_29_2","first-page":"193","volume-title":"Translation in Eukaryotes","author":"Jackson R J","year":"1991","unstructured":"R J Jackson Translation in Eukaryotes, ed H Trachsel (CRC, Boca Raton, FL), pp. 193\u2013229 (1991)."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75852-9"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.29.17423"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.tb18752.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)70365-2"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(79)81339-3"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48413-X"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.9.2703"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.2.554"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.46.070177.000441"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.15.1.138-144.1977"},{"key":"e_1_3_3_40_2","first-page":"R445","volume":"268","author":"Frerichs K U","year":"1995","unstructured":"K U Frerichs, G Dienel, L Sokoloff, J M Hallenbeck Am J Physiol 268, R445\u2013R453 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_41_2","first-page":"R1507","volume":"37","author":"Srere H K","year":"1995","unstructured":"H K Srere, D Belke, L C H Wang, S L Martin Am J Physiol 37, R1507\u2013R1512 (1995).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.15.7119"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(96)00494-5"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/334170a0"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2894-4_21"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7648"},{"key":"e_1_3_3_47_2","first-page":"R895","volume":"267","author":"Anchordoguy T J","year":"1994","unstructured":"T J Anchordoguy, S C Hand Am J Physiol 267, R895\u2013R900 (1994).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67052005.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.24.14511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:56:41Z","timestamp":1649865401000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.24.14511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,11,24]]},"references-count":48,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1998,11,24]]}},"alternative-id":["10.1073\/pnas.95.24.14511"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.24.14511","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,11,24]]},"assertion":[{"value":"1998-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-09-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-11-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}