The Role of Lysosomes and Microtubules in Cardiac Protein Degradation

Wildenthal, K.; Crie, J. S.; Ord, J. M.; Wakeland, J. R.

doi:10.1007/978-1-4757-1287-2_10

Cited by 8 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meerson et al (1978) found that cardiac protein degradation in rats 23-24 months old was significantly lower than that in rats 3-4 months old. Similarly, Wildenthal & Crie (1980) observed a decreased rate of cardiac protein degradation in rats aged 1-14 months compared to those 1-2 months old. In contrast, Barrows & Roeder (1961) found no change in the rate of cardiac protein degradation in rats I 2 and 24 months old.…”

Section: ( B ) Protein Degradation In Tissues and Organsmentioning

confidence: 69%

Protein Synthesis and Degradation During Aging and Senescence

Makrides

1983

Biological Reviews

171

View full text Add to dashboard Cite

Summary 1. The published results on protein synthesis during aging are contradictory. Possible sources of error and variability include: an insufficient number of different animal ages used; use of whole organs that are cytologically highly heterogeneous; different animal strains; neglecting to measure the specific activity of the precursor pool for protein synthesis; and inadequate methodology for measurement of in vivo rates of protein synthesis. 2. In general, protein synthesis rates in mammals have been reported to decline 4–70% with age. In insects and other organisms, greater losses (60–90%) have been observed. 3. Limited evidence indicates that in some systems a decline in the rate of protein synthesis may be due to alterations (as yet of unknown nature) in the initiation components of the protein synthetic apparatus. Futhermore, some studies suggest that in some organisms aging affects the expression of specific parts of the genome. 4. The significance of results on protein metabolism obtained from some studies with nematodes is at present unknown, owing to problems associated with age‐synchronization methods. Also, the in vitro fibroblast system for the study of human cellular aging has not been met with universal acceptance; it is generally believed that this system has not yet been established as a valid analogy to mammalian aging in vivo. 5. Failure to detect defective enzymes in many old organisms indicates at least that not all proteins are altered during aging. The complete thermal stability of purified enzymes from old organisms suggests that the observed thermolability of the same enzymes in crude cell extracts is not an intrinsic property of those enzymes. Post‐translational modifications (partial denaturation) may constitute the primary mechanism for the production of altered cell polypeptides during aging. 6. The available evidence does not support the concept of an age‐dependent decline in translational accuracy. The future purification to absolute homogeneity of an altered enzyme and its ‘young’ (unaltered) counterpart, and their sequencing, should resolve the question of translational errors. 7. Some degree of age‐related ribosome loss appears to occur in fixed postmitotic cells. In general, the published polyribosomal profiles may represent artefacts due to insufficiently suppressed ribonuclease activity during extraction. 8. The published studies on protein degradation during aging are also contradictory. Some investigators have neglected the possibility of reutilization of labelled amino acid. It is possible that some of the observed age‐related alterations in protein degradation rates are due to altered endocrine status of the animals used, rather than to defects in the protein degradative pathways. The studies utilizing cell culture systems are also contradictory, probably due to different experimental designs. 9. Limited evidence suggests that protein degradation may slow down with age in mammals and nematodes. An inefficient protein degradation system in old organisms could provide a...

show abstract

Section: ( B ) Protein Degradation In Tissues and Organsmentioning

confidence: 69%

Protein Synthesis and Degradation During Aging and Senescence

Makrides

1983

Biological Reviews

171

View full text Add to dashboard Cite

show abstract

“…tabolism of specific intracellular proteins has not been established (Dean, 1975;Wildenthal and Crie, 1980). It is well known, however, that proteins entering cells by endocytosis are degraded in lysosomes (Gorden et al, 1978;Goldstein et al, 1979;Pittman et al, 1979) and that enhanced proteolysis, induced by nutritional deprivation (Neely et al, 1977;Amenta and Sargus, 1979) or by certain hormones (DeMartino and Goldberg, 1978;Wildenthal and Crie, 1980), involves lysosomal proteinases. In addition, lysosomes have been implicated in pathologic states, including the breakdown of neuronal (Hirsch et al, 1974;Dixit et al, 1981;Chelmicka-Schorr et al, 1982) and glial (Einstein et al, 1972;Rauch et a!., 1973) proteins.…”

Section: Discussionmentioning

confidence: 99%

Degradation of Neurofilament Proteins by Purified Human Brain Cathepsin D

Nixon

Marotta

1984

Journal of Neurochemistry

View full text Add to dashboard Cite

Cathepsin D (CD) was purified to homogeneity from postmortem human cerebral cortex. Incubation of CD with human neurofilament proteins (NFPs) prepared by axonal flotation led to the rapid degradation of the 200,000, 160,000, and 70,000 NFP subunits (200K, 160K, and 70K) which had been separated by one- or two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Degradation was appreciable at enzyme activity-to-substrate protein ratios that were two- to threefold lower than those in unfractionated homogenates from cerebral cortex. Quantitative measurements of NFPs separated by PAGE revealed that, at early stages of digestion, the 160K NFP was somewhat more rapidly degraded than the 70K subunit while the 200K NFP had an intermediate rate of degradation. At sufficiently high enzyme concentrations, all endogenous proteins in human NF preparations were susceptible to the action of CD. Human brain CD also degraded cytoskeletal proteins in NF preparations from mouse brain with a similar specificity. To identify specific NFP break-down products, antisera against each of the major NFPs were applied to nitrocellulose electroblots of NFPs separated by two-dimensional SDS-PAGE. In addition to detecting the 200K, 160K, and 70K NFP in human NF preparations, the antisera also detected nonoverlapping groups of polypeptides resembling those in NF preparations from fresh rat brain. When human NF preparations were incubated with CD, additional polypeptides were released in specific patterns from each NFP subunit. Some of the immuno-cross-reactive fragments generated from NFPs by CD comigrated on two-dimensional gels with polypeptides present in unincubated preparations. These results demonstrate that NFPs and other cytoskeletal proteins are substrates for CD. The physiological significance of these findings and the possible usefulness of analyzing protein degradation products for establishing the action of proteinases in vivo are discussed.

show abstract

“…Inhibiting lysosome function in the heart results in an approximately 25-30% reduction in the overall rate of protein degradation 17 . While lysosome activity does not appear to affect myosin degradation, it does play a role in the degradation of organellar proteins, including mitochondrial cytochromes and microtubules 17, 18 . Autophagy, which is involved with targeted lysosomal degradation of proteins and organelles, occurs constitutively at a low level during normal cardiac function 19 .…”

Section: Introductionmentioning

confidence: 99%

Tear Me Down

Patterson

Portbury

Schisler

et al. 2011

Circulation Research

View full text Add to dashboard Cite

Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize the molecular mechanisms by which calpain inhibition has been shown to modulate the development of cardiac (specifically ventricular) hypertrophy. The context within which calpain inhibition might be developed for therapeutic intervention of cardiac hypertrophy is then discussed.

show abstract

The Role of Lysosomes and Microtubules in Cardiac Protein Degradation

Cited by 8 publications

References 16 publications

Protein Synthesis and Degradation During Aging and Senescence

Protein Synthesis and Degradation During Aging and Senescence

Degradation of Neurofilament Proteins by Purified Human Brain Cathepsin D

Tear Me Down

Contact Info

Product

Resources

About