Initiation of protein synthesis and heat-shock protein-72 expression in the rat brain following severe insulin-induced hypoglycemia.
Following stress such as heat shock or transient cerebral ischemia, global brain protein synthesis initiation is depressed through modulation of eucaryotic initiation factor (eIF) activities, and modification of ribosomal subunits. Concomitantly, expression of a certain class of mRNA, heat-shock protein (HSP) mRNA, is induced. Here we report that the activity of eucaryotic initiation factor-2 (eIF-2), a protein that participates in the regulation of a rate-limiting initiation step of protein synthesis, transiently decreases following insulin-induced severe hypoglycemia in the rat brain neocortex. Expression of HSP 72, a 72-kDa HSP, in surviving neurons was seen at 1-7 days of recovery following 30 min of hypoglycemic coma, but not at 1 h and 6 h of recovery. In the neocortex, HSP 72 was first seen in layer IV, and later also in surviving neurons in layer II. In the CA1 region and in the crest of dentate gyrus, HSP 72 expression was evident in cells adjacent to irreversibly damaged neurons. In the CA3 region and the hilus of dentate gyrus, HSP 72 was expressed in a few scattered neurons. In septal nucleus, HSP 72 was expressed in a lateral to medial fashion over a period of 1-3 days of recovery. We conclude that severe insulin-induced hypoglycemia induces a stress response in neurons in the recovery phase, including inhibition of protein synthesis initiation, depression of eIF-2 activity, and a delayed and prolonged expression of HSP 72 in surviving neurons. The HSP 72 expression may be a protective response to injurious stress.
Bergstedt
K
K
Laboratory for Experimental Brain Research, Lund University, Lund Hospital, Sweden.
Hu
B R
BR
Wieloch
T
T
D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects*; D003926:Diabetic Coma / Q000378:metabolism / Q000473:pathology; D015852:Eukaryotic Initiation Factor-2 / Q000096:biosynthesis; D005947:Glucose / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000276:immunology; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007328:Insulin; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D012358:RNA, Transfer, Met / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000648:ultrastructure; D013462:Sulfur Radioisotopes
D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D012358:RNA, Transfer, Met; D013462:Sulfur Radioisotopes; D005947:Glucose