Lockwood T D
Department of Pharmacology and Toxicology, School of Medicine, Wright State University, Dayton, OH 45435.
Biochem J. 1988 Apr 15;251(2):341-6. doi: 10.1042/bj2510341.
In the Langendorff isolated perfused rat heart, 36% of total basal protein degradation was inhibited by the lysosomal inhibitor chloroquine (30 microM), after elimination of rapid turnover proteins during a 3 h preliminary degradation period. Prior inhibition of degradation with chloroquine was additive to the 30% inhibition caused by simultaneous infusion of 50-200 nM-isoprenaline. This additivity suggests that the adrenergic-controlled process is independent of the lysosomal degradative pathway. After discontinuation of drug infusions, the isoprenaline-inhibited degradation rate returned to the previous baseline; however, the chloroquine-inhibited degradation rate transiently exceeded the previous baseline. NaN3 (0.3 mM) caused a decrease of left-ventricular myocardial ATP content of approx. 60% at 14 min and extreme impairment of contractile function; however, the total lysosomal and non-lysosomal protein degradation was not changed at this time. Conversely, left-ventricular tissue ATP content was not changed during proteolytic inhibition by 10 nM-isoprenaline or 10 microM-chloroquine at 14 min. The results indicate that depletion of myocardial energy stores in this preparation is neither necessary nor sufficient to cause inhibition of the total of lysosomal and non-lysosomal protein degradation.
在Langendorff离体灌注大鼠心脏中，在3小时的预降解期消除快速周转蛋白后，溶酶体抑制剂氯喹（30微摩尔）抑制了36%的基础蛋白总降解。预先用氯喹抑制降解与同时输注50 - 200纳摩尔异丙肾上腺素所引起的30%的抑制作用具有相加性。这种相加性表明肾上腺素能控制的过程独立于溶酶体降解途径。停止药物输注后，异丙肾上腺素抑制的降解速率恢复到先前的基线；然而，氯喹抑制的降解速率短暂超过先前的基线。叠氮化钠（0.3毫摩尔）在14分钟时使左心室心肌ATP含量降低约60%，并使收缩功能严重受损；然而，此时溶酶体和非溶酶体蛋白的总降解没有变化。相反，在14分钟时，10纳摩尔异丙肾上腺素或10微摩尔氯喹抑制蛋白水解过程中，左心室组织ATP含量没有变化。结果表明，在此制剂中，心肌能量储备的耗尽对于抑制溶酶体和非溶酶体蛋白的总降解既非必要条件也非充分条件。
