Gene Expression and Protein Degradation

Remmen, Holly Van; Ward, Walter F.; Sabia, Robert V.; Richardson, Arlan

doi:10.1002/cphy.cp110109

Cited by 58 publications

(47 citation statements)

References 390 publications

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“…Proper proteome dynamics are critical to normal development and maintenance of health (7,8). For example, the dysregulation of protein turnover has been implicated in the aging process (9), increased degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is a primary cause of cystic fibrosis (10), and the inability to clear protein aggregates leads to pathogenic accumulations in Alzheimer's, Parkinson's, Creutzfeldt-Jakob, and other age-related diseases (11).…”

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confidence: 99%

Analysis of proteome dynamics in the mouse brain

Price

Guan²,

Burlingame³

et al. 2010

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

335

447

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Fig. 2. (A)Interaction web of top-down and bottom-up effects in the eelgrass study system. The top predator is the sea otter (E. lutris), the mesopredators are crabs (Cancer spp. and Pugettia producta), the epiphyte mesograzers are primarily an isopod (I. resecata) and a sea slug (P. taylori), and algal epiphyte competitors of eelgrass primarily consist of chain-forming diatoms, and the red alga Smithora naiadum. Solid arrows indicate direct effects, dashed arrows indicate indirect effects, and the plus and minus symbols indicate positive and/or negative effects on trophic guilds and eelgrass condition. C, competitive interaction; T, trophic interaction. (Original artwork by A. C. Hughes.) (B-E) Survey results testing for the effects of sea otter density on eelgrass bed community properties (Tables S2 and S3). Elkhorn Slough (sea otters present and high nutrients) eelgrass beds (n = 4) are coded in red, and the Tomales Bay reference site (no sea otters, low nutrients) beds (n = 4) are coded in blue. (B) Crab biomass and size structure of two species of Cancer crabs; (C) grazer biomass per shoot and large grazer density; (D) algal epiphyte loading; and (E) aboveground and belowground eelgrass biomass. DW, dry weight; FW, fresh weight.

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mentioning

confidence: 99%

Analysis of proteome dynamics in the mouse brain

Price

Guan²,

Burlingame³

et al. 2010

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

335

447

View full text Add to dashboard Cite

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“…Virtually all cross-sectional studies of mammalian aging have been interpreted as though they were performed longitudinally (e.g. see the studies and discussion of the studies in Van Remmen et al ., 1995). The effects of LTCR are almost always assumed to have resulted from incremental resistance to essentially irreversible damage.…”

Section: Widespread Views Of Aging Have Slowed the Development Of Lonmentioning

confidence: 99%

Use of microarray biomarkers to identify longevity therapeutics

Spindler

2006

Aging Cell

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SummaryA number of lines of evidence, including nonhuman primate and human studies, suggest that regulatory pathways similar to those invoked by caloric restriction (CR) may be involved in determining human longevity. Thus, pharmaceuticals capable of mimicking the molecular mechanisms of life-and health-span extension by CR (CR mimetics) may have application to human health. CR acts rapidly, even in late adulthood, to begin to extend life-and health-span in mice. We have linked these effects with rapid changes in the levels of specific gene transcripts in the liver and the heart. Our results are consistent with the rapid effects of caloric intake on the lifespan and/or biochemistry and physiology of Drosophila , rodents, rhesus macaques and humans. To test the hypothesis that existing pharmaceuticals can mimic the physiologic effects of CR, we evaluated the effectiveness of glucoregulatory drugs and putative cancer chemopreventatives in reproducing the hepatic gene-expression profiles produced by long-term CR (LTCR). We found that 8 weeks of metformin treatment was superior to 8 weeks of CR at reproducing the specific changes in transcript levels produced by LTCR. Consistent with these results, metformin reduces cancer incidence in diabetic humans and ameliorates the onset and severity of metabolic syndrome. Metformin extends the mean and maximum lifespans of female transgenic HER-2/neu mice by 8% and 13.1% in comparison with control mice. Phenformin, a close chemical relative of metformin, extends lifespan and reduces tumor incidence in C3H mice. These results indicate that gene-expression biomarkers can be used to identify promising candidate CR mimetics.

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“…A general age-associated decline in the function of multiple proteins has been correlated with several types of posttranslational modifications, particularly oxidation, glycation, isomerization, deamidation, racemization, and cross-linking (1)(2)(3). Although the exact processes leading to the increase in these dysfunctional proteins remains undefined, it has been suggested that the greater accumulation of such modifications with age may result, at least in part, from the diminished capacity of the cell for the removal and replacement of defective proteins.…”

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confidence: 99%

“…However, a number of studies also report conflicting results, due perhaps to the complications inherent in measurements of total protein turnover, which represent weighted averages from a complex mixture of turnover rates (reviewed in Ref. 3). …”

mentioning

confidence: 99%

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Altered Turnover of Calcium Regulatory Proteins of the Sarcoplasmic Reticulum in Aged Skeletal Muscle

Ferrington

Krainev

Bigelow

1998

Journal of Biological Chemistry

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We have measured the in vivo protein turnover for the major calcium regulatory proteins of the sarcoplasmic reticulum from the skeletal muscle of young adult (7 months) and aged (28 months) Fischer 344 rats. From the time course of the incorporation and decay of proteinassociated radioactivity after a pulse injection of [ 14 C]leucine and correcting for leucine reutilization, in young rats, the apparent half-lives for calsequestrin, the 53-kDa glycoprotein, and ryanodine receptor are 5.4 ؎ 0.4, 6.3 ؎ 1.3, and 8.3 ؎ 1.3 days, respectively. A half-life of 14.5 ؎ 2.5 days was estimated for the Ca-ATPase isolated from young muscle. Differences in protein turnover associated with aging were determined using sequential injection of two different isotopic labels ([ 14 C]leucine and [ 3 H]leucine) to provide an estimate of protein synthesis and degradation within the same animal. The Ca-ATPase and ryanodine receptor isolated from aged muscle exhibits 27 ؎ 5% and 25 ؎ 3% slower protein turnover, respectively, relative to that from young muscle. In contrast, the 53-kDa glycoprotein exhibits a 25 ؎ 5% more rapid turnover in aged SR, while calsequestrin exhibits no age-dependent alteration in turnover. Statistical analysis comparing the sensitivity of various methods for discriminating different rates of protein turnover validates the approach used in this study and demonstrates that the use of two isotopic labels provides at least a 6-fold more sensitive means to detect age-related differences in protein turnover relative to other methods.A general age-associated decline in the function of multiple proteins has been correlated with several types of posttranslational modifications, particularly oxidation, glycation, isomerization, deamidation, racemization, and cross-linking (1-3). Although the exact processes leading to the increase in these dysfunctional proteins remains undefined, it has been suggested that the greater accumulation of such modifications with age may result, at least in part, from the diminished capacity of the cell for the removal and replacement of defective proteins. In agreement with this hypothesis, total protein turnover in a number of tissues has been reported to decrease with age. However, a number of studies also report conflicting results, due perhaps to the complications inherent in measurements of total protein turnover, which represent weighted averages from a complex mixture of turnover rates (reviewed in Ref. 3).In the present study, we have addressed the possibility that altered protein turnover may be responsible for the diminished skeletal muscle contractile properties observed with age that are directly attributable to SR 1 proteins involved in excitationcontraction coupling, e.g. the Ca-ATPase and the calcium release channel (the ryanodine receptor) (4, 5). In the case of the Ca-ATPase, which mediates the rate-limiting resequestration of calcium into the SR lumen, oxidative modifications have been implicated in the observed age-related loss of heat stability and concomitant conformatio...

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Gene Expression and Protein Degradation

Cited by 58 publications

References 390 publications

Analysis of proteome dynamics in the mouse brain

Analysis of proteome dynamics in the mouse brain

Use of microarray biomarkers to identify longevity therapeutics

Altered Turnover of Calcium Regulatory Proteins of the Sarcoplasmic Reticulum in Aged Skeletal Muscle

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