Identification of the bioactive peptide PEC-60 in brain

Norberg, Åke; Gruber, Susanne; Angelucci, Francesco; Renlund, Staffan; Wadensten, Henrik; Efendić, Suad; Östenson, Claes Göran; Jörnvall, Hans; Sillard, Rannar; Mathé, Aleksander A.

doi:10.1007/s000180300030

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…However, the down-regulation of the protease inhibitor Kazal type 4 (gastrointestinal peptide, PEC-60) in HT-29 cells in response to elevated zinc levels is interesting with respect to its proposed functions. This 60 amino-acid peptide has been originally isolated form the gastrointestinal tract but is also expressed in neurons (Fuxe et al 1994, Norberg et al 2003. The primary function of PEC-60 derived from the gastrointestinal tract is thought to be the inhibition of insulin secretion (Agerberth et al 1989, Ahren et al 1992.…”

Section: Discussionmentioning

confidence: 99%

Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells

et al. 2005

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High cellular zinc concentrations lead to impairments in ATP synthesis and cell cycle control particularly in neurons and epithelial cells. The molecular basis for these dysfunctions is still not fully elucidated. Here we analyzed the effects of a high zinc exposure (10 ppm) on gene and protein expression in the human epithelial cell line HT-29. Of the 1176 genes analyzed with cDNA arrays, nine differentially expressed genes were identified. Proteome analysis based on 1310 detected proteins identified 11 molecular targets. Most of the identified genes/proteins have not been linked to cellular zinc status before (e.g. PEC-60, R-ras3). More than half of the targets participate in ATP production or stress response. Therefore, it appears that higher zinc concentrations mediate their effects mainly via impairments in cellular energy metabolism and stress response.

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Section: Discussionmentioning

confidence: 99%

Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells

et al. 2005

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“…It has been reported that brain metastatic cells from breast cancer and lung cancer induce large amounts of serine protease inhibitors (SERPINs) to prevent plasminogen activator (PA) destruction of L1CAM and mediate the spread of metastatic cells [ 43 ]. SPINK4 has also been demonstrated to play a role in the brain [ 44 ]. Nevertheless, more studies are required to verify whether SPINK4 can activate L1CAM through PA inhibition to drive metastasis and CCRT resistance in rectal cancer.…”

Section: Discussionmentioning

confidence: 99%

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

et al. 2021

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Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p < 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p < 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p < 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.

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“…SPINK2 (located on 4q12) is expressed in the testis, epididymis, and seminal vesicle, where its antimicrobial function may be involved in protection of fertility (Rockett et al 2004). SPINK4 was originally isolated from pig intestine (Agerberth et al 1989) and is abundantly expressed in human and porcine goblet cells in the crypts of Lieberkühn but was also found in monocytes and in the central nervous system (Metsis et al 1992; Norberg et al 2003). SPINK5 is expressed in the thymus, vaginal epithelium, Bartolin’s glands, oral mucosa, tonsils, and the parathyroid glands (Magert et al 1999).…”

Section: Introductionmentioning

confidence: 99%

The SPINK gene family and celiac disease susceptibility

et al. 2007

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The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n=15) and diet-treated patients (n=31) and controls (n=16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population.

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Identification of the bioactive peptide PEC-60 in brain

Cited by 4 publications

References 11 publications

Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells

Effects of increased cellular zinc levels on gene and protein expression in HT-29 cells

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

The SPINK gene family and celiac disease susceptibility

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