Intracellular protein catabolism: state of the art

Mayer, R. John; Doherty, Fergus J.

doi:10.1016/0014-5793(86)80403-3

Cited by 90 publications

(31 citation statements)

References 164 publications

(49 reference statements)

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“…Of these two genes, cathepsin L gene expression appeared to be associated with glucose intolerance, because an inverse correlation was seen between cathepsin L gene expression and plasma glucose across all groups of mice at 3 and 15 months. Cathepsin L is a ubiquitously expressed lysosomal cysteine proteinase and is primarily responsible for intracelluar protein degradation (22). It has been ascribed a key role in T-cell selection in the thymus (23) and in skin metabolism and hair formation (24).…”

Section: Discussionmentioning

confidence: 99%

Impaired Cathepsin L Gene Expression in Skeletal Muscle Is Associated With Type 2 Diabetes

Huang

Vaag²,

Carlsson

et al. 2003

Diabetes

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To identify abnormally expressed genes associated with muscle insulin resistance or type 2 diabetes, we screened the mRNA populations using cDNA differential display combined with relative RT-PCR analysis from muscle biopsies of diabetes-prone C57BL/6J and diabetes-resistant NMRI mice fed with a high-fat or normal diet for 3 or 15 months. Six abnormally expressed genes were isolated from the mice after a 3-month fat feeding; one of them was cathepsin L. No significant difference in mRNA levels of these genes was observed between fatand normal-diet conditions in either strains. However, cathepsin L mRNA levels in muscle were higher in normal diet-fed C57BL/6J mice compared with normal diet-fed NMRI mice at 3 months (0.72 ؎ 0.04 vs. 0.51 ؎ 0.04 relative units, P < 0.01, n ‫؍‬ 8 -10) and at 15 months (0.41 ؎ 0.05 vs. 0.27 ؎ 0.04 relative units, P ‫؍‬ 0.01, n ‫؍‬ 9 -10). Further, cathepsin L mRNA levels in muscle correlated inversely with plasma glucose in both strains regardless of diets at 3 (r ‫؍‬ ؊0.49, P < 0.01, n ‫؍‬ 31) and 15 (r ‫؍‬ ؊0.42, P ‫؍‬ 0.007, n ‫؍‬ 39) months. To study whether cathepsin L plays a role in human diabetes, we measured cathepsin L mRNA levels in muscle biopsies taken before and after an insulin clamp from 12 monozygotic twin pairs discordant for type 2 diabetes and from 12 control subjects. Basal cathepsin L mRNA levels were not significantly different between the study groups. Insulin infusion increased cathepsin L mRNA levels in control subjects from 1.03 ؎ 0.30 to 1.90 ؎ 0.32 relative units (P ‫؍‬ 0.03). Postclamp cathepsin L mRNA levels were lower in diabetic twins but similar in nondiabetic twins compared with control subjects (0.66 ؎ 0.22, 1.16 ؎ 0.18 vs. 1.38 ؎ 0.21 relative units, P < 0.02, NS, respectively). Further, postclamp cathepsin L mRNA levels were correlated with insulin-mediated glucose uptake (r ‫؍‬ 0.37, P ‫؍‬ 0.03), particularly, with glucose oxidation (r ‫؍‬ 0.37, P ‫؍‬ 0.03), and fasting glucose concentrations (r ‫؍‬ ؊0.45, P < 0.01) across all three study groups. In conclusion, muscle cathepsin L gene expression is increased in diabetes-prone mice and related to glucose tolerance. In humans, insulin-stimulated cathepsin L expression in skeletal muscle is impaired in diabetic but not in nondiabetic monozygotic twins, suggesting that the changes may be secondary to impaired glucose metabolism. Diabetes 52:2411-2418, 2003 I nsulin resistance can be induced by high-fat intake in animals and humans (1-4) and is seen at the levels of whole-body and skeletal muscle (4,5). The degree of fat-induced insulin resistance varies according to different genetic backgrounds in humans (6) and in experimental animals (7-10). The C57BL/6J mouse is genetically prone to develop insulin resistance and diabetes. When challenged with a high-fat diet, the C57BL/6J mouse shows elevated plasma insulin and glucose levels compared with a control mouse strain (8,10). Therefore, strain-specific and fat-responsive genes could contribute to insulin resistance and glucose intolerance in C57BL/6J...

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Section: Discussionmentioning

confidence: 99%

Impaired Cathepsin L Gene Expression in Skeletal Muscle Is Associated With Type 2 Diabetes

Huang

Vaag²,

Carlsson

et al. 2003

Diabetes

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“…at steady state, rates of protein synthesis and degradation are equal. Although turnover of protein results in energy dissipation, regulation at the level of protein degradation effectively controls protein levels (Paskin & Mayer, 1977;Mayer & Doherty, 1986).…”

Section: Introductionmentioning

confidence: 99%

Untitled

Blommaart

1997

The Histochemical Journal

204

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SummaryThe rate of proteolysis is an important determinant of the intracellular protein content. Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy. In liver, macroautophagy is very active and almost completely accounts for starvation-induced proteolysis. Factors inhibiting this process include amino acids, cell swelling and insulin. In the mechanisms controlling macroautophagy, protein phosphorylation plays an important role. Activation of a signal transduction pathway, ultimately leading to phosphorylation of ribosomal protein S6, accompanies inhibition of macroautophagy. Components of this pathway may include a heterotrimeric G i3 -protein, phosphatidylinositol 3-kinase and p70S6 kinase. Recent evidence indicates that lysosomal protein degradation can be selective and occurs via ubiquitin-dependent and -independent pathways.

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“…[7,8]) and particularly within the red blood cell [9,10]. ATP has been reported to have a small activating effect upon the lysosomal aspartic proteinase, cathepsin D [11].…”

Section: Introductionmentioning

confidence: 99%

Stabilisation of cathepsin E by ATP

Thomas¹,

Richards²,

Jupp³

et al. 1989

FEBS Letters

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The hydrolysis of 3 distinct substrates by cathepsin E from human red blood cells and gastric mucosa was measured in the presence and absence of physiologically relevant concentrations of ATP. At pH values below about 5.0, the nucleotide was without effect. However, at pH 5.8, whereas cathepsin E was virtually inactive by itself, it was restored to full activity (k~O by ATP and the non-hydrolysable methylene-ATP analogue. At still higher pH values, k~t progressively diminished but significant levels of cathepsin E activity were readily detectable at pH 7.0. The specificity of this stabilisation effect was examined.

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Intracellular protein catabolism: state of the art

Cited by 90 publications

References 164 publications

Impaired Cathepsin L Gene Expression in Skeletal Muscle Is Associated With Type 2 Diabetes

Impaired Cathepsin L Gene Expression in Skeletal Muscle Is Associated With Type 2 Diabetes

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Stabilisation of cathepsin E by ATP

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