Pipkin J L, Hinson W G, Lyn-Cook L E, Duffy P H, Feuers R J, Leakey J E, Aly K B, Hart R W, Casciano D A
Division of Genetic Toxicology, National Center For Toxicological Research, Jefferson, Arkansas 72079-9502, USA.
Aging (Milano). 1996 Oct;8(5):311-9. doi: 10.1007/BF03339587.
The synthesis ([35S]-incorporation) of stress proteins (sps, i.e., 24, 25, 70, 90 Mr) and of nuclear protein 48 (p48) was investigated in the heart and bone marrow cells of three groups of male Fischer 344 rats following administration of isoproterenol (IPR). Two groups of rats, young ad libitum (Y/AL-3 1/2 months) and old/AL (O/AL-28 months), had full access to rat chow; a third group of old diet restricted (O/DR-28 months) rats was maintained on a diet restricted intake of 40% of the Y/AL animals. Sp synthesis in the bone marrow (25, 70, 90 Mr) and heart (24, 70, 90 Mr) nuclei of O/AL was significantly reduced, as compared with Y/AL and O/DR rats, following their induction with IPR. A unique sp24 was expressed in heart following IPR dosing. A 1 mg/kg dose of IPR was lethal for O/AL, but not for Y/AL or O/DR animals. This lethal dose induced synthesis of p48 in heart and bone marrow nuclei of O/AL rats only. P48 existed in isoform states in bone marrow, and when a lethal dose of IPR was administered in this tissue, it was expressed in O/AL rats in a cell-cycle regulated pattern. Stress proteins and other non-sps were seen as cell cycle regulated following IPR administration. P48 in bone marrow and heart nuclei from O/AL rats showed an antigenic response identical to that of p48 in HL60 nuclei. The presence of p48 is correlated with mortality and with an ad libitum diet in old rats, since it is absent in old diet restricted animals; therefore, DR may impede the expression of p48 through a mechanism(s) that is undisclosed at this time.
在三组雄性Fischer 344大鼠的心脏和骨髓细胞中，研究了给予异丙肾上腺素（IPR）后应激蛋白（sps，即分子量为24、25、70、90kDa）和核蛋白48（p48）的合成（[35S]掺入）情况。两组大鼠，即自由摄食的年轻大鼠（Y/AL - 3.5个月）和老年自由摄食大鼠（O/AL - 28个月），可随意获取大鼠饲料；第三组老年限食大鼠（O/DR - 28个月）的饮食摄入量限制为Y/AL组动物的40%。与Y/AL组和O/DR组大鼠相比，O/AL组大鼠经IPR诱导后，其骨髓（分子量为25、70、90kDa）和心脏（分子量为24、70、90kDa）细胞核中的sp合成显著减少。IPR给药后，心脏中表达了一种独特的sp24。1mg/kg剂量的IPR对O/AL组大鼠具有致死性，但对Y/AL组或O/DR组动物无致死性。该致死剂量仅诱导O/AL组大鼠心脏和骨髓细胞核中p48的合成。P48在骨髓中以同工型状态存在，当在该组织中给予致死剂量的IPR时，它在O/AL组大鼠中以细胞周期调节模式表达。给予IPR后，应激蛋白和其他非sps表现为细胞周期调节。O/AL组大鼠骨髓和心脏细胞核中的P48显示出与HL60细胞核中p48相同的抗原反应。P48的存在与老年大鼠的死亡率和自由摄食饮食相关，因为在老年限食动物中不存在；因此，限食可能通过目前尚未揭示的机制阻碍p48的表达。
