Effect of ambient oxygen concentration on lipofuscin accumulation in cultured rat heart myocytes—A novel in vitro model of lipofuscinogenesis

Sohal, Rajindar S.; Marzabadi, Massoud R.; Galaris, Dimitrios; Brunk, Ulf T.

doi:10.1016/0891-5849(89)90155-x

Cited by 89 publications

(49 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two MRL strains, which exhibited no lipofuscin, were relatively resistant to lesion formation. Based on these observations, as well as data reported by others suggesting that both lipofuscin (1)(2)(3)(4)(5)(6)(7)(8)(9) and fatty streak (26) formation involve lipid oxidation, we hypothesized that these processes may exhibit coordinate control. To investigate this hypothesis, we examined the concordance of lipofuscin and fatty streak formation in ATH-fed BALB/cJ mice, which exhibit incomplete penetrance of both traits.…”

Section: Methodsmentioning

confidence: 99%

“…Oxidative stress appears to play a key role in lipofuscin formation. For example, increases in oxygen and iron concentrations act synergistically to induce lipofuscin deposition in cultured rat myocytes (4,5). Similarly, high intake ofpolyunsaturated fatty acids (6) or deficiency ofantioxidants, such as vitamin E (7,8 ), increases the rate of lipofuscin formation in tissues of experimental animals.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

Qiao

Welch²,

Xie³

et al. 1993

J. Clin. Invest.

View full text Add to dashboard Cite

Lipofuscin pigment, a terminal oxidation product, accumulates within cells during the normal aging process and under certain pathological conditions. We have analyzed a genetic cross between two inbred mouse strains, BALB/cJ and a subline of C57BL/6J, which differ in lipofuscin deposition. A comparison of the segregation pattern of cardiac lipofuscin with the albino locus (c) on mouse chromosome 7 revealed complete concordance. Analysis of spontaneous mutants of the tyrosinase gene, encoded by the albino locus, confirmed that the tyrosinase gene itself controls lipofuscin formation. Genetic analysis of other strains indicated that one or more additional genes can contribute to the inheritance of lipofuscin. We also present evidence for an association between cardiac lipofuscin deposition and aortic fatty streak development in the mouse. (J. Clin. Invest. 1993. 92:2386-2393

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

Qiao

Welch²,

Xie³

et al. 1993

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Cells are usually exposed to a higher oxygen tension in vitro (51) than in vivo (52) and this could induce high levels of basal lipid peroxidation, which in turn may lead to a high constitutive collagen gene expression. When myocardial cells are exposed to higher oxygen tensions they have a parallel increase in lipofuscin (53) which is thought to be a product of lipid peroxidation (54). However, under the conventional incubation conditions (95% air/5% C02) used in our experiments, and in the absence ascorbic acid, the level oflipid peroxidation found in our cultured human fibroblasts is comparable with that in cultured myocardial cells (280+30 pmol/mg protein) (55) and in normal skin (21,22) and other tissues in vivo (Houglum, K., unpublished observations; 19,20,29).…”

Section: Discussionmentioning

confidence: 99%

d-alpha-tocopherol inhibits collagen alpha 1(I) gene expression in cultured human fibroblasts. Modulation of constitutive collagen gene expression by lipid peroxidation.

Houglum¹,

Brenner²,

Chojkier³

1991

J. Clin. Invest.

114

View full text Add to dashboard Cite

Ascorbic acid stimulates collagen gene transcription in cultured fibroblasts, and this effect is mediated through the induction of lipid peroxidation by ascorbic acid. Quiescent cultured fibroblasts in the absence of ascorbic acid have a high constitutive level of collagen production, but the mechanisms of collagen gene regulation in this unstimulated state are not known. Because lipid peroxidation also occurs in normal cells, we wondered if lipid peroxidation plays a role in the regulation of basal collagen gene expression. Inhibition of lipid peroxidation in cultured human fibroblasts with d-a-tocopherol or methylene blue decreased the synthesis ofcollagen, the steady-state levels of procollagen al(I) mRNA and the transcription of the procollagen al(I) gene. This effect on collagen gene expression was selective and not associated with cellular toxicity. Thus, these experiments suggest a role for lipid peroxidation in the modulation of constitutive collagen gene expression. (J. Clin. Invest.

show abstract

“…In all cases, senescence was associated with accumulations of oxidized and/or ubiquitinated proteins, substrates for the proteasome (22,116,144). Moreover, it has been shown that when fibroblasts (211,222) and cardiomyocytes (198) are either loaded with or induced to form lipofuscin, they assume a senescent phenotype and are more susceptible to oxidative injury.…”

Section: Proteasome Dysfunction In Senescent Cardiomyocyte Lossmentioning

confidence: 99%

The ubiquitin-proteasome system in cardiac physiology and pathology

Powell

2006

American Journal of Physiology-Heart and Circulatory Physiology

144

118

View full text Add to dashboard Cite

The ubiquitin-proteasome system (UPS) is the major nonlysosomal pathway for intracellular protein degradation, generally requiring a covalent linkage of one or more chains of polyubiquitins to the protein intended for degradation. It has become clear that the UPS plays major roles in regulating many cellular processes, including the cell cycle, immune responses, apoptosis, cell signaling, and protein turnover under normal and pathological conditions, as well as in protein quality control by removal of damaged, oxidized, and/or misfolded proteins. This review will present an overview of the structure, biochemistry, and physiology of the UPS with emphasis on its role in the heart, if known. In addition, evidence will be presented supporting the role of certain muscle-specific ubiquitin protein ligases, key regulatory components of the UPS, in regulation of sarcomere protein turnover and cardiomyocyte size and how this might play a role in induction of the hypertrophic phenotype. Moreover, this review will present the evidence suggesting that proteasomal dysfunction may play a role in cardiac pathologies such as myocardial ischemia, congestive heart failure, and myofilament-related and idiopathic-dilated cardiomyopathies, as well as cardiomyocyte loss in the aging heart. Finally, certain pitfalls of proteasome studies will be described with the intent of providing investigators with enough information to avoid these problems. This review should provide current investigators in the field with an up-to-date analysis of the literature and at the same time provide an impetus for new investigators to enter this important and rapidly changing area of research.

show abstract

Effect of ambient oxygen concentration on lipofuscin accumulation in cultured rat heart myocytes—A novel in vitro model of lipofuscinogenesis

Cited by 89 publications

References 14 publications

Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

Involvement of the tyrosinase gene in the deposition of cardiac lipofuscin in mice. Association with aortic fatty streak development.

d-alpha-tocopherol inhibits collagen alpha 1(I) gene expression in cultured human fibroblasts. Modulation of constitutive collagen gene expression by lipid peroxidation.

The ubiquitin-proteasome system in cardiac physiology and pathology

Contact Info

Product

Resources

About