A Possible Explanation of Myxedema and Hypercholesterolemia
in Hypothyroidism: Control of Lysosomal
Hyaluronidase and Cholesterol Esterase by Thyroid Hormones

DeMartino, George N.; Goldberg, Alfred L.

doi:10.1159/000459140

Cited by 21 publications

(4 citation statements)

References 22 publications

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“…Lysosomal proteases are responsible for degradation of endocytosed proteins including membrane proteins (24)(25)(26). The cytosolic proteases -calpain and m-calpain trigger proteolytic cleavage of target proteins (frequently in response to phosphorylation events) (27); calpain-dependent cleavage may either clear the target protein or, on occasion, lead to the generation of stable proteolytic intermediates with gain-of-function activity. The ubiquitin-proteasome system is a major ATP-dependent pathway for protein degradation in muscle, particularly for myofibrillar proteins that comprise the majority of muscle proteins.…”

Section: Discussionmentioning

confidence: 99%

Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I

Kedar

McDonough

Arya

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

295

245

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Muscle-specific RING finger protein 1 (MuRF1) is a sarcomereassociated protein that is restricted to cardiac and skeletal muscle. In skeletal muscle, MuRF1 is up-regulated by conditions that provoke atrophy, but its function in the heart is not known. The presence of a RING finger in MuRF1 raises the possibility that it is a component of the ubiquitin-proteasome system of protein degradation. We performed a yeast two-hybrid screen to search for interaction partners of MuRF1 in the heart that might be targets of its putative ubiquitin ligase activity. This screen identified troponin I as a MuRF1 partner protein. MuRF1 and troponin I were found to associate both in vitro and in vivo in cultured cardiomyocytes. MuRF1 reduced steady-state troponin I levels when coexpressed in COS-7 cells and increased degradation of endogenous troponin I protein in cardiomyocytes. The degradation of troponin I in cardiomyocytes was associated with the accumulation of ubiquitylated intermediates of troponin I and was proteasome-dependent. In vitro, MuRF1 functioned as a ubiquitin ligase to catalyze ubiquitylation of troponin I through a RING finger-dependent mechanism. In isolated cardiomyocytes, MuRF1 reduced indices of contractility. In cardiomyocytes, these processes may determine the balance between hypertrophic and antihypertrophic signals and the regulation of myocyte contractile responses in the setting of heart failure.

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Section: Discussionmentioning

confidence: 99%

Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I

Kedar

McDonough

Arya

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

295

245

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“…3) The cytosol also contains two Ca 2ϩ -activated proteases, calpainand -m, whose in vivo function in normal cells remains unclear (28). The precise roles of all these degradative systems in the breakdown of different muscle proteins are yet to be determined.…”

mentioning

confidence: 99%

Importance of the ATP-Ubiquitin-Proteasome Pathway in the Degradation of Soluble and Myofibrillar Proteins in Rabbit Muscle Extracts

Solomon

Goldberg

1996

Journal of Biological Chemistry

Self Cite

363

288

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Recent studies have suggested that activation of the ubiquitin-proteasome pathway is primarily responsible for the rapid loss of muscle proteins in various types of atrophy. The present studies were undertaken to test if different classes of muscle proteins are degraded by this pathway. In extracts of rabbit psoas muscle, the complete degradation of soluble proteins to amino acids was stimulated up to 6-fold by ATP. Peptide aldehyde inhibitors of the proteasome or the removal of proteasomes markedly inhibited only the ATP-dependent process. Addition of purified myosin, actin, troponin, or tropomyosin to these extracts showed that these proteins served as substrates for the ubiquitin-proteasome pathway. By contrast, degradation of myoglobin did not require ATP, proteasomes, or any known proteases in muscles.When myosin, actin, and troponin were added as actomyosin complexes or as intact myofibrils to these extracts, they were not hydrolyzed at a significant rate, probably because in these multicomponent complexes, these proteins are protected from degradation. Accordingly, actin (but not albumin or troponin) inhibited the degradation of 125 I-myosin, and actin was found to selectively inhibit ubiquitin conjugation to 125 I-myosin. Also, the presence of tropomyosin inhibited the degradation of 125 I-troponin. However, neither actin nor tropomyosin inhibited the degradation of 125 I-lysozyme or soluble muscle proteins. Thus, specific interactions between the myofibrillar proteins appear to protect them from ubiquitin-dependent degradation, and the ratelimiting step in their degradation is probably their dissociation from the myofibril.

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“…(Table 3) Myxedema in hypothyreosis (usually generalized) (Table 4) For generalized myxedema, an impaired degradation of glycosaminoglycans has been considered (2). In thyroidectomized rats, the activity of the lysosomal enzymes as hyaluro- Diagnostie only in pronouneed nidase but also cholesterol esterase is reduced to 4()-5()% in connective tisue (10). This could account for the accumulation of glycosaminoglycans in the dermis as well as the increased cholesterol levels.…”

Section: Staining Of Mucinous Compoundsmentioning

confidence: 96%

“…Mucobla.st (transformed fibroblast) in plaquelike form of cutaneous nuicinosis. Mucinous material inside and outside the niueoplast (X 60(10).…”

mentioning

confidence: 99%

Cutaneous mutinous deposits

Steigleder¹,

B²

1985

J Cutan Pathol

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A survey of conditions with mucinous deposits is given. The most important factors for their diagnosis are to consider these disorders and to stain the slides for proteoglycans or glycosaminoglycans; the most common routine techniques are the Giemsa and the Alcian-blue stain. More sophisticated methods allow differentiation between specific compounds, especially hyaluronic acid and various proteoglycans.

show abstract

A Possible Explanation of Myxedema and Hypercholesterolemia in Hypothyroidism: Control of Lysosomal Hyaluronidase and Cholesterol Esterase by Thyroid Hormones

Cited by 21 publications

References 22 publications

Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I

Muscle-specific RING finger 1 is a bona fide ubiquitin ligase that degrades cardiac troponin I

Importance of the ATP-Ubiquitin-Proteasome Pathway in the Degradation of Soluble and Myofibrillar Proteins in Rabbit Muscle Extracts

Cutaneous mutinous deposits

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