Proteome profiling of aging in mouse models: Differential expression of proteins involved in metabolism, transport, and stress response in kidney

Chakravarti, Bulbul; Seshi, Beerelli; Ratanaprayul, Wongrat; Dalal, Neville; Li, Lin; Raval, Alpan; Chakravarti, Deb N.

doi:10.1002/pmic.200700208

Cited by 22 publications

(18 citation statements)

References 51 publications

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“…Collectively, these changes can be interpreted as an increase in protein damage with age being counterbalanced by diminished protein synthesis and inadequate PQC. Similar changes in proteostasis have been reported for mammals; aged mice show decreased levels of mitochondrial proteins, proteins involved in defence against oxidative stress, and chaperones involved in the stress response [60][61][62] . In addition, ageing of human der mal fibroblasts ex vivo is also associated with reduced levels of chaperone, proteasomal, ribosomal, and mitochondrial proteins 22 .…”

Section: Derailment During Normal Ageingsupporting

confidence: 72%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

141

126

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The worldwide increase in life expectancy gives rise to an increasing prevalence of cardiac diseases, which remain the leading cause of disability and death in the developed world [1][2][3] . Currently, the mechanisms under lying how ageing contributes to the initiation or acceler ation of cardiac diseases are essentially unresolved. Prevailing theories of ageing centre on gradual derail ment of cellular protein homeostasis -proteostasis -either by design (genetically) or by 'wear and tear' (environmentally) 3 . Central to the role of proteostasis derailment as a major factor in ageing is the observation that protein function declines over time.Proteins are the most versatile and complex macro molecules and are involved in the proper functioning of every biological process 4 . After synthesis as a poly peptide chain from the genetic code, proper function of a protein relies heavily on its correct folding into a 3D native state and on various post translational modifi cations, mostly involving the addition of chem ical groups (including phosphate, acetate, and carbo hydrate). Protein maturation, transport, and ultimately breakdown is monitored and supported by various classes of proteins, collectively called 'protein quality control' (PQC) [3][4][5] . Balanced proteostasis, therefore, depends on proper PQC and is crucial for cellular and organismal health 6 . The intricate network making up the PQC involves numerous proteins, of which the main players are the chaperones and their regula tors 4,7-9 (assisting in folding and refolding of proteins) and the pathways that clear irreversibly misfolded and aggregation prone proteins (the ubiquitin-proteasome system [UPS] and autophagy systems) 9-11 . With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 . Importantly, evidence indicates that the amount of soluble, aggregate prone protein oligomers, rather than the abundance of pro tein aggregates, correlates with disease severity 23,24 . Therefore, protein aggregates, which contain both misfolded proteins and elevated levels of chaper ones, constitute an adequate PQC response, aimed at sequestering potentially harmful protein oligomers, rather than embodying the ultimate cellular threat 25 . This ...

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Section: Derailment During Normal Ageingsupporting

confidence: 72%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

141

126

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“…The protein expression of 59 proteins was found to be significantly altered out of which 49 proteins increased in older mice. The majority of significantly altered proteins were involved in OXPHOS, TCA cycle, propanoate metabolism, transport mechanisms (albumin, transferrin), unfolded protein response (UPR; glucose-regulated protein 78, VCP), and aldehyde detoxification (Chakravarti et al, 2009). The glucose-regulated protein 78 (GRP78), also known as immunoglobulin heavy-chain binding protein (BiP), was found increased in the kidney of old mice.…”

Section: Kidneymentioning

confidence: 99%

“…To gain insight into molecular mechanisms involved in kidney ageing, the proteome of C57/BL6 mice kidneys was investigated using 2-D PAGE and LC-MS/MS (Chakravarti et al, 2009). Male mice between 19-22 weeks and 24 months of age were used.…”

Section: Kidneymentioning

confidence: 99%

Proteome analysis in the assessment of ageing

Nkuipou‐Kenfack

Koeck

Mischak

et al. 2014

Ageing Research Reviews

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“…Many more studies used cell lines derived from various nephron regions with the major limitation that it remains unclear how far these cell lines reflect the in-vivo situation 88 . Most studies have applied proteomics to study disease processes using whole kidney tissue as material 55,[89][90][91][92][93][94] . Obviously, this approach is simple and fast but has major limitations due to the morphological diversity and complexity of the kidney.…”

Section: Application Of Proteomics To Normal and Diseased Kidney Funcmentioning

confidence: 99%

“…Specialized software converts the MS and MS/MS spectra into a 12 ageing-related protein expression changes in a mouse kidney based on the 2D gel technology 55 , to the peptide-based (phospho)proteome analysis of isolated nephron segments or their in vitro cellular models using LC-MS/MS analysis 25,26,31,43,46 .…”

Section: Data Processing and Analysismentioning

confidence: 99%

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

Velić

Maček

Wagner

2010

Seminars in Nephrology

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AcknowledgementsResearch in the laboratories of the authors has been supported by grants from the Minstry of Science, Baden-Wuerttenberg (to BM) and the Swiss National Science Foundation, the 6 th and 7 th EU Framework projects (EuReGene and EUNEFRON) (to CAW). We thank MatthiasMann for critically reading and discussing the manuscript. Summary 2Organs are complex structures that consist of multiple tissues with different levels of gene expression. To achieve a comprehensive coverage and accurate quantitation data, organs should ideally be separated into morphological and/or functional substructures prior to gene or protein expression analysis. However, due to complex morphology and elaborate isolation protocols, this was so far often difficult to achieve. Kidneys are organs where functional and morphological subdivision is especially important. Each subunit of the kidney, the nephron, itself consists of more than 10 subsegments with distinct morphological and functional characteristics. For a full understanding of kidney physiology, global gene and protein expression analyses have to be performed at the level of the nephron subsegments; however, such studies have so far been extremely rare.Here we describe the latest approaches in quantitative high accuracy mass spectrometrybased proteomics and their application to quantitative proteomics studies of the whole kidney and nephron subsegments, both in humans and in animal models. We compare these studies with similar studies performed on other organ substructures. We argue that the newest technologies used for preparation, processing and measurement of small amounts of starting material are finally enabling global and subsegment-specific quantitative measurement of protein levels in the kidney and other organs. These new technologies and approaches are making a decisive impact on our understanding of the (patho)physiological processes at the molecular level.3

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Proteome profiling of aging in mouse models: Differential expression of proteins involved in metabolism, transport, and stress response in kidney

Cited by 22 publications

References 51 publications

Proteostasis in cardiac health and disease

Proteostasis in cardiac health and disease

Proteome analysis in the assessment of ageing

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

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