Protein Profiling of the Human Epidermis from the Elderly Reveals Up-regulation of a Signature of Interferon-γ-induced Polypeptides That Includes Manganese-superoxide Dismutase and the p85β Subunit of Phosphatidylinositol 3-Kinase

Gromov, Pavel; Skovgaard, Gunhild Lange; Pálsdóttir, Hildur; Gromova, Irina; Østergaard, Morten; Celis, Julio E.

doi:10.1074/mcp.m200051-mcp200

Cited by 40 publications

(28 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, older human skin expresses reduced levels of certain proteins, including manganese-superoxide dismutase, tryptophanyl-tRNA synthetase, the p85ß subunit of phosphatidylinositol 3-kinase, and proteasomal proteins PA28-α (Gromov et al 2003). In rats, peroxiredoxin-2, an antioxidant enzyme, is able to be induced by irradiation in cultured astrocytes from young but less so from old rats (Miura et al 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Proteomic techniques including two-dimensional gel electrophoresis (2-DE) have been used to study aging (Ballesteros et al 2001;Gromov et al 2003;Sato et al 2006;Miura et al 2007) and have led to the identification of many candidate proteins that are altered by aging. For example, older human skin expresses reduced levels of certain proteins, including manganese-superoxide dismutase, tryptophanyl-tRNA synthetase, the p85ß subunit of phosphatidylinositol 3-kinase, and proteasomal proteins PA28-α (Gromov et al 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma biomarkers of mouse aging

Ding

Kopchick

2010

AGE

View full text Add to dashboard Cite

Normal aging is accompanied by a series of physiological changes such as gray hair, cataracts, reduced immunity, and increased susceptibility to disease. To identify novel biomarkers of normal aging, we analyzed plasma proteins of male mice longitudinally from 2 to 19 months of age. Plasma proteins were analyzed by two-dimensional gel electrophoresis and identified using mass spectrometry (MS), MS/MS and liquid chromatography MS/MS. We found that many plasma proteins exist as multiple isoforms with different masses and/or charges. Thirty-nine protein spots (corresponding to six distinct proteins) have been identified, 13 of which exhibited significant changes with age. For example, several proteins increased significantly during aging including one isoform of transthyretin, two isoforms of haptoglobin, and three isoforms of immunoglobulin kappa chain. Conversely, several proteins decreased significantly during aging including peroxiredoxin-2, serum amyloid protein A-1, and five isoforms of albumin. Identification of these proteins provides new biomarkers of normal aging in mice. If validated in humans, these biomarkers may facilitate therapeutic interventions to identify premature aging, delay aging, and/or improve healthspan of the elderly.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasma biomarkers of mouse aging

Ding

Kopchick

2010

AGE

View full text Add to dashboard Cite

show abstract

“…Furthermore, we previously reported that the radiation adaptive response observed in the astrocytes of young rats is suppressed in aged rats, indicating that the response of astrocytes to low-dose radiation decreases with age [12]. Thus, we tried to clarify the response of astrocytes to oxidative stress and its variation with age through proteomic analysis.Proteomic analysis offers great potential for studies on cellular protein alterations in various disease states [13][14][15], aging [16][17][18][19], and under oxidative stress [20][21][22][23][24]. Unlike genomic and transcriptional profiling, proteomic Age-dependent variation in cell responses to oxidative stress 2787 profiles can detect not only native proteins but also posttranslational modified species, which are the functional components in biological systems.…”

mentioning

confidence: 99%

Age‐dependent variations of cell response to oxidative stress: Proteomic approach to protein expression and phosphorylation

et al. 2005

View full text Add to dashboard Cite

We investigated the protein profiles of variously aged rat astrocytes in response to oxidative stress. After H2O2-exposure of cells at 100 microM for 30 min, the relative intensity of ten protein spots changed on two-dimensional (2-D) gels compared with control gels after silver staining. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis after in-gel digestion revealed that six of these spots corresponded to three kinds of proteins, each of which was composed of a protein and its modified form with a different isoelectric point (pI). These three proteins were identified as peroxiredoxins (PRDXs) II and III, and calpactin I light chain (p11). H2O2-exposure increased the intensity of the spot with lower pI and simultaneously decreased that of the spot with higher pI for both PRDXs II and III. In addition, the expression of annexin VII, S-adenosyl-L-homocysteine hydrolase, elongation factor II fragment (EF-II), and adenosine deaminase was increased by H2O2-exposure in astrocytes from variously aged rats. Using the Pro-Q Diamond staining, heat shock protein 60 kDa (Hsp 60) and alpha-tubulin were observed to be phosphorylated upon H2O2-exposure. While phosphorylation of alpha-tubulin was correlated positively with age, the changes in abundance of ten protein spots as described above were independent of age. These results suggest that aging does not suppress the responses aimed at limiting injury and promoting repair brought about by severe oxidative stress, and might affect cell dynamics including the formation of microtubules.

show abstract

“…Nine of the genes are down-regulated in BRCA2-ablated cells whereas five of them are up-regulated ( Table 1). Majority of the down-regulated genes are known to be regulated by interferons, e.g., tryptophanyl-tRNA synthetase, UCRP, UBE2L6, and Cig5 [22][23][24][25][26]. Interferons enhance cellular susceptibility to apoptosis in a variety of tumor cells [27].…”

Section: Down-regulation Of Ucrp Ube2l6 and Other Transcripts In Brmentioning

confidence: 99%

Down-regulation of UCRP and UBE2L6 in BRCA2 knocked-down human breast cells

Tripathi

Chaudhuri

2005

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

To understand the effects of the transient ablation of BRCA2 gene expression in dividing human breast cells we transiently knocked down BRCA2 mRNA in HMEC and other cells. Microarray analysis of mRNAs revealed the down-regulation of the mRNAs of ubiquitin cross-reacting protein (UCRP) and the E2 enzyme that help conjugating UCRP to its target proteins, namely UBE2L6 (UbcH8), in BRCA2 ablated cells. UCRP is an interferon regulated protein, involved in cell growth and cell cycle events by participating in the degradation/modulation of cell cycle regulatory proteins. Quantitative-PCR and Northern analysis confirmed down-regulation of UCRP and UBE2L6 with BRCA2 knock down, respectively. Since UCRP and UCRPylation have critical roles in the innate immunity against viral infection and during pregnancy, our observation may indicate new roles of the BRCA2 protein. KeywordsBRCA2; UCRP; ISG15; UBE2L6; UbcH8; siRNA; shRNA; H1 RNA promoter; Antisense phosphorothioate; Microarray BRCA2 is a tumor suppressor protein with diverse functions [1,2]. BRCA2 deficiency has been attributed as the cause for many cases of breast, ovarian, and pancreatic carcinoma [1,2]. BRCA2 deficiency may be caused by the molecular defects in the BRCA2 genes or due to sporadic reasons. BRCA2 gene is not expressed in non-dividing cells and the rate of expression of this protein is increased with the rate of cell proliferation [3][4][5]. This growth dependent turn-on/turn-off mechanism of this gene is not well understood. Any number of environmental cues may influence the turn-on event and may initiate a molecular domino effect leading to DNA damage and oncogenesis. While undue expression of BRCA2 protein in non-dividing cells may initiate apoptosis, failure of the cell to produce appropriate amount of BRCA2 corresponding to the growth rate of the cell may also be detrimental. Since majority of the breast cancer cases are sporadic [1][2][3][4][5], some of such cancers may have initiated due to the transient absence of BRCA2 during the proliferative stages of the breast cells.The molecular consequences of transient BRCA2 deficiency in the breast cells are not known. We report here our preliminary observations on the effect of transient ablation of BRCA2 gene expression on human mammary epithelial cells (HMEC) and BT549 human breast carcinoma cells. Microarray analysis of the mRNAs isolated from these BRCA2 knocked down cells showed a limited number of genes that are down-regulated as an Materials and methods Knockdown of BRCA2 gene expressionWe took three parallel approaches for the transient knock down of BRCA2 gene expression.In one, we used anti-BRCA2 antisense gapmer oligonucleotides (sense control: 5′-ATGCCTATTGGATCCAA-3′; antisense: 5′-TTGGATCCAATAGGCAT-3′). In the gapmer (custom synthesized from Tri-link Biotechnology, CA) the terminal five nucleotides have 2-methoxy ribose and the middle 7 nucleotides are phosphorothioate. These oligos were used previously [13,14] to knock down BRCA2 in human cells. In the second approach, we used BRCA2...

show abstract

Protein Profiling of the Human Epidermis from the Elderly Reveals Up-regulation of a Signature of Interferon-γ-induced Polypeptides That Includes Manganese-superoxide Dismutase and the p85β Subunit of Phosphatidylinositol 3-Kinase

Cited by 40 publications

References 108 publications

Plasma biomarkers of mouse aging

Plasma biomarkers of mouse aging

Age‐dependent variations of cell response to oxidative stress: Proteomic approach to protein expression and phosphorylation

Down-regulation of UCRP and UBE2L6 in BRCA2 knocked-down human breast cells

Contact Info

Product

Resources

About