Proteasome alterations during adipose differentiation and aging: links to impaired adipocyte differentiation and development of oxidative stress
| Autor: | Jeffrey N. Keller, Luke I. Szweda, Sun Ok Fernandez-Kim, Kalavathi Dasuri, Le Zhang, Annadora J. Bruce-Keller, Philip J. Ebenezer |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Proteasome Endopeptidase Complex medicine.medical_specialty Cellular differentiation Adipose tissue Biology medicine.disease_cause Biochemistry Article Mice chemistry.chemical_compound 3T3-L1 Cells Physiology (medical) Adipocyte Internal medicine Adipocytes medicine Animals Cellular Senescence Ubiquitin Cell Differentiation Mice Inbred C57BL Oxidative Stress Endocrinology Adipose Tissue chemistry Proteasome Adipogenesis Cell aging Oxidative stress Homeostasis |
| Zdroj: | Free Radical Biology and Medicine. 51:1727-1735 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2011.08.001 |
| Popis: | Intracellular proteins are degraded by a number of proteases including the ubiquitin-proteasome pathway (UPP). Impairments in the UPP occur during the aging of a variety of tissues, although little is known in regards to age-related alterations to the UPP during the aging of adipose tissue. The UPP is known to be involved in regulating the differentiation of a variety of cell types, although the potential changes in UPP during adipose differentiation have not been fully elucidated. Simultaneously elucidating how the UPP is altered in aging adipose tissue and adipocyte differentiation, and determining the effects of proteasome inhibition on adipocyte homeostasis and differentiation, are critical issues to elucidate experimentally. Adipogenesis continues throughout the life of adipose tissue, with continual differentiation of pre-adipocytes essential to maintaining tissue function during aging, while UPP alterations in mature adipocytes is likely to directly modulate adipose function during aging. In the current study we demonstrate that aging induces alterations in the activity and expression of principal components of the UPP. Additionally, we show that multiple changes in the UPP occur during the differentiation of 3T3-L1 cells into adipocytes. In vitro data link observed UPP alterations to increased levels of oxidative stress and altered adipose biology relevant to both aging and differentiation. Taken together, these data demonstrate that changes in the UPP occur in response to adipose aging and adipogenesis, and strongly suggest that proteasome inhibition is sufficient to decrease adipose differentiation, as well as increase oxidative stress in mature adipocytes, both of which likely promote deleterious effects on adipose aging. |
| Databáze: | OpenAIRE |
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