Vcsa1 Gene Peptides for the Treatment of Inflammatory and Allergic Reactions

Morris, Katherine; Kuo, Byron; Wilkinson, Mark; Davison, Joseph S.; Befus, A. Dean; Mathison, Ronald

doi:10.2174/187221307780979892

Cited by 12 publications

(13 citation statements)

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“…The predominant molecular form of CABS1 was detected at 27 kDa, and additional immunoreactive bands were also identified between 12 and 20 kDa and between 33 and 90 kDa in a small (13/99 and 10/99, respectively) number of participants. We originally identified CABS1 in human salivary gland extracts (71) during our search for a human protein with a sequence similarity to the anti-inflammatory peptide sequence near the carboxy terminus of the rat prohormone, SMR1 (36,44). The Smr1 gene we studied in rats is not present in humans, and although sequence similarity for other peptides derived from Smr1 with analgesic or erectile function activities had been identified in human PROL1 and SMR3A and SMR3B genes (73,74,79), the human gene with a sequence similar to the anti-inflammatory sequence from Smr1 was unknown.…”

Section: Discussionmentioning

confidence: 99%

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1)

Ritz

Rosenfield

Laurent

et al. 2017

American Journal of Physiology-Regulatory, Integrative and Comp

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Calcium-binding protein spermatid-specific 1 (CABS1) is expressed in the human submandibular gland and has an anti-inflammatory motif similar to that in submandibular rat 1 in rats. Here, we investigate CABS1 in human saliva and its association with psychological and physiological distress and inflammation in humans. Volunteers participated across three studies: ) weekly baseline measures;) a psychosocial speech and mental arithmetic stressor under evaluative threat; and ) during academic exam stress. Salivary samples were analyzed for CABS1 and cortisol. Additional measures included questionnaires of perceived stress and negative affect; exhaled nitric oxide; respiration and cardiac activity; lung function; and salivary and nasal inflammatory markers. We identified a CABS1 immunoreactive band at 27 kDa in all participants and additional molecular mass forms in some participants. One week temporal stability of the 27-kDa band was satisfactory (test-retest reliability estimate = 0.62-0.86). Acute stress increased intensity of 18, 27, and 55 kDa bands; 27-kDa increases were associated with more negative affect and lower heart rate, sympathetic activity, respiration rate, and minute ventilation. In both acute and academic stress, changes in 27 kDa were positively associated with salivary cortisol. The 27-kDa band was also positively associated with VEGF and salivary leukotriene B4 levels. Participants with low molecular weight CABS1 bands showed reduced habitual stress and negative affect in response to acute stress. CABS1 is readily detected in human saliva and is associated with psychological and physiological indicators of stress. The role of CABS1 in inflammatory processes, stress, and stress resilience requires careful study.

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Section: Discussionmentioning

confidence: 99%

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1)

Ritz

Rosenfield

Laurent

et al. 2017

American Journal of Physiology-Regulatory, Integrative and Comp

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“…It is processed also into other bioactive peptides, namely heptapeptide with the sequence TDIFEGG, named submandibular gland peptide-T and its C-terminal derivative, tripeptide FEG. The last mentioned above peptides are considered as regulators of inflammatory and allergic reactions in various animal models (Mathison et al 2010 ; Morris et al 2007 ). Sialorphin is released locally and systematically from SMR 1 protein.…”

Section: Inhibitors Of Enkephalin-degrading Enzymesmentioning

confidence: 99%

“…Rougeot et al ( 2003 ) have provided evidence that sialorphin is a natural inhibitor of the cell surface NEP in several mammals models. This indicates the lack of species-specific activity, similar to TDIFEGG peptide (Morris et al 2007 ). It has been demonstrated that this peptide acts as a competitive inhibitor of renal and spinal NEP, inhibiting the degradation of substance P and Met 5 -enkephalin and thus displaying analgesic activity (Rougeot et al 2003 ).…”

Section: Inhibitors Of Enkephalin-degrading Enzymesmentioning

confidence: 99%

Opioids, Neutral Endopeptidase, its Inhibitors and Cancer: Is There a Relationship among them?

Mizerska-Dudka

Kandefer‐Szerszeń

2014

Arch. Immunol. Ther. Exp.

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The role of endogenous animal opioids in the biology of cancer is widely recognized but poorly understood. This is, among others, because of the short half-life of these peptides, which are quickly inactivated by endopeptidases, e.g., neutral endopeptidase (NEP, CD10). It has been established that NEP is engaged in the modulation of the tumor microenvironment, among others that of colon cancer, by exerting influence on cell growth factors, the extracellular matrix and other biologically active substances. Although there are some discrepancies among the findings on the role of both opioids and NEP in cancer development, authors agree that their role seems to depend on the origin, stage and grade of tumor, and even on the method of examination. Moreover, recently, natural inhibitors of NEP, such as sialorphin, opiorphin and spinorphin have been detected. Their analgesic activity has been established. It is interesting to ask whether there is a relationship among opioid peptides, tumor-associated NEP and its inhibitors.

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“…Before considering the pharmacology of SGP-T and its analogues a brief summary of the VCSa1 gene family and its products is presented as this subject was recently reviewed [24]. …”

Section: Bioactivity Of Salivary Gland Extracts: Sgp-tmentioning

confidence: 99%

“…The VCSA family, containing the Vcsa1 gene, has emerged recently, and exclusively in rodents, whereas the proline-rich VCSB family is found in all placental mammals [27]. Human members of the VCSB family include PROL1 , SMR3B (PROL3) , and SMR3A (PROL5) [24], and encode salivary and lacrimal secreted proline-rich proteins [28-30]. The SMR1 protein product of the rat Vcsa1 gene is cleaved into at least two biologically active peptides, sialorphin (QHNPR) and SGP-T (TDIFEGG) (Figure 3).…”

Section: The Vcsa1 Gene Familymentioning

confidence: 99%

Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein

Mathison

Davison

Befus

et al. 2010

Journal of Inflammation

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The limitations of steroidal and non steroidal anti-inflammatory drugs have prompted investigation into other biologically based therapeutics, and identification of immune selective anti-inflammatory agents of salivary origin. The traditional view of salivary glands as accessory digestive structures is changing as their importance as sources of systemically active immunoregulatory and anti-inflammatory factors is recognized. Salivary gland involvement in maintenance of whole body homeostasis is regulated by the nervous system and thus constitutes a "neuroendocrine axis". The potent anti-inflammatory activities, both in vivo and in vitro, of the tripeptide Phe-Glu-Gly (FEG) are reviewed. FEG is a carboxyl terminal peptide of the prohormone SMR1 identified in the rat submandibular salivary gland, The D-isomeric form (feG) mimics the activity of its L-isomer FEG. Macropharmacologically, feG attenuates the cardiovascular and inflammatory effects of endotoxemia and anaphylaxis, by inhibition of hypotension, leukocyte migration, vascular leak, and disruption of pulmonary function and intestinal motility. Mechanistically, feG affects activated inflammatory cells, especially neutrophils, by regulating integrins and inhibiting intracellular production of reactive oxygen species. Pharmacodynamically, feG is active at low doses (100 μg/kg) and has a long (9-12 hour) biological half life. As a therapeutic agent, feG shows promise in diseases characterized by over exuberant inflammatory responses such as systemic inflammatory response syndrome and other acute inflammatory diseases. Arthritis, sepsis, acute pancreatitis, asthma, acute respiratory inflammation, inflammatory bowel disease, and equine laminitis are potential targets for this promising therapeutic peptide. The term "Immune Selective Anti-Inflammatory Derivatives" (ImSAIDs) is proposed for salivary-derived peptides to distinguish this class of agents from corticosteroids and nonsteroidal anti-inflammatory drugs.

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Vcsa1 Gene Peptides for the Treatment of Inflammatory and Allergic Reactions

Cited by 12 publications

References 0 publications

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1)

A novel biomarker associated with distress in humans: calcium-binding protein, spermatid-specific 1 (CABS1)

Opioids, Neutral Endopeptidase, its Inhibitors and Cancer: Is There a Relationship among them?

Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein

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