Systematic comparison of the human saliva and plasma proteomes

Department of Biological Chemistry, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA
PROTEOMICS - CLINICAL APPLICATIONS (Impact Factor: 2.96). 12/2008; 3(1):116 - 134. DOI: 10.1002/prca.200800140


The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides. To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released. A total of 1939 nonredundant salivary proteins were compiled from a total of 19 474 unique peptide sequences identified from whole and ductal salivas; 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma. The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics.

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Available from: Mireya Gonzalez
    • "This research, however, is still limited to cataloging the microbiome [Zaura, 2012] , without providing an understanding of the processes that underlie the adaptability and resilience of the system. Similarly , saliva research has been revitalized due to the availability of advanced 'omics' technologies [Yan et al., 2009;. In contrast, much less well studied are the host factors, including immunological aspects contributing to oral health [Curtis et al., 2011] . "
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    ABSTRACT: During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term ‘oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain microbial community stability in health. However, the oral ecosystem itself is not stable: throughout life an individual undergoes multiple physiological changes while progressing through infancy, childhood, adolescence, adulthood and old age. Recent discussions on the definition of general health have led to the proposal that health is the ability of the individual to adapt to physiological changes, a condition known as allostasis. In this paper the allostasis principle is applied to the oral ecosystem. The multidimensionality of the host factors contributing to allostasis in the oral cavity is illustrated with an example on changes occurring in puberty. The complex phenomenon of oral health and the processes that prevent the ecosystem from collapsing during allostatic changes in the entire body are far from being understood. As yet individual components (e.g. hard tissues, microbiome, saliva, host response) have been investigated, while only by consolidating these and assessing their multidimensional interactions should we be able to obtain a comprehensive understanding of the ecosystem, which in turn could serve to develop rational schemes to maintain health. Adapting such a ‘system approach' comes with major practical challenges for the entire research field and will require vast resources and large-scale multidisciplinary collaborations.
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    • "Thus, high throughput proteomics holds promise for disease-associated biomarker identification [157] and substantial progress has been made in the proteomic analysis of saliva through a combination of sophisticated approaches to protein separation and advances in mass spectrometry technology [157, 158]. The salivary proteome has now been identified; it contains some 1166 proteins [159] and proteomic studies confirm the commonality of the salivary proteome and plasma proteins [159, 160]. Proteomic approaches have already identified salivary biomarkers of both Sjogren's syndrome and oral cancer [19, 161, 162]. "
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    ABSTRACT: Periodontitis is a chronic inflammatory condition of the tissues that surround and support the teeth and is initiated by inappropriate and excessive immune responses to bacteria in subgingival dental plaque leading to loss of the integrity of the periodontium, compromised tooth function, and eventually tooth loss. Periodontitis is an economically important disease as it is time-consuming and expensive to treat. Periodontitis has a worldwide prevalence of 5-15% and the prevalence of severe disease in western populations has increased in recent decades. Furthermore, periodontitis is more common in smokers, in obesity, in people with diabetes, and in heart disease patients although the pathogenic processes underpinning these links are, as yet, poorly understood. Diagnosis and monitoring of periodontitis rely on traditional clinical examinations which are inadequate to predict patient susceptibility, disease activity, and response to treatment. Studies of the immunopathogenesis of periodontitis and analysis of mediators in saliva have allowed the identification of many potentially useful biomarkers. Convenient measurement of these biomarkers using chairside analytical devices could form the basis for diagnostic tests which will aid the clinician and the patient in periodontitis management; this review will summarise this field and will identify the experimental, technical, and clinical issues that remain to be addressed before such tests can be implemented.
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    • "With the salivary proteome including thousands of non-redundant proteins identified (Loo et al, 2010), it is clear that their functions are diverse and many, as is reflected in the significant body of original work, as well as that summarized in several recent outstanding review articles. Some of these resources are listed below, and the reader is encouraged to refer to them especially on the subjects of the functions of saliva (Aps and Martens, 2005; Groschl, 2009; Salles et al, 2011); the composition of the salivary proteome (Groschl, 2008; Yan et al, 2009; Loo et al, 2010); and diagnostics values of saliva (Malamud, 2011; Pfaffe et al, 2011; Spielmann and Wong, 2011; Schapher et al, 2011). The subject of the current review, on the other hand, is less explored and it is related to a small but prominent category of salivary peptides – hormonal modulators of energy intake and output , hereafter referred to as metabolic hormones. "
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    ABSTRACT: The salivary proteome consists of thousands of proteins, which include, among others, hormonal modulators of energy intake and output. Although the functions of this prominent category of hormones in whole body energy metabolism are well characterized, their functions in the oral cavity, whether as a salivary component, or when expressed in taste cells, are less studied and poorly understood. The respective receptors for the majority of salivary metabolic hormones have been also shown to be expressed in salivary glands (SGs), taste cells, or other cells in the oral mucosa. This review provides a comprehensive account of the gastrointestinal hormones, adipokines, and neuropeptides identified in saliva, SGs, or lingual epithelium, as well as their respective cognate receptors expressed in the oral cavity. Surprisingly, few functions are assigned to salivary metabolic hormones, and these functions are mostly associated with the modulation of taste perception. Because of the well-characterized correlation between impaired oral nutrient sensing and increased energy intake and body mass index, a conceptually provocative point of view is introduced, whereupon it is argued that targeted changes in the composition of saliva could affect whole body metabolism in response to the activation of cognate receptors expressed locally in the oral mucosa.
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