Distinction between major chloroquine-inhibitable and adrenergic-responsive pathways of protein degradation and their relation to tissue ATP content in the Langendorff isolated perfused rat heart.
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.
Lockwood
T D
TD
Department of Pharmacology and Toxicology, School of Medicine, Wright State University, Dayton, OH 45435.
D019297:2,4-Dinitrophenol; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001386:Azides / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology*; D004140:Dinitrophenols / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D019810:Sodium Azide
D001386:Azides; D004140:Dinitrophenols; D011506:Proteins; D002738:Chloroquine; D000255:Adenosine Triphosphate; D019810:Sodium Azide; D007930:Leucine; D007545:Isoproterenol; D019297:2,4-Dinitrophenol