Human Kallikrein 3 (prostate-specific antigen) and Human Kallikrein 5                     Expression in Salivary Gland Tumors

Darling, Mark; Tsai, S.; Jackson-Boeters, Linda; Daley, Tom D.; Diamandis, Eleftherios P.

doi:10.1177/172460080602100401

Cited by 5 publications

(2 citation statements)

References 29 publications

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“…In fact, salivary glands are expected to have low protein levels of this kallikrein (approximately 33.9 ppm), according to the PAXdb database ( Table S1 ). Moreover, the expression of human Klk3 was not detected in normal salivary gland tissue nor in salivary gland tumors, using immunohistochemistry assays [ 52 ]. However, using in situ hybridization, Klk3-encoding transcripts were detected in the serous epithelial cells of submandibular glands [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Exposure to Supraphysiological Levels of Testosterone Impacts Rat Submandibular Gland Proteome

Valente-Santos,

Vitorino,

Sousa-Mendes

et al. 2023

IJMS

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The salivary glands play a central role in the secretion of saliva, whose composition and volume affect oral and overall health. A lesser-explored dimension encompasses the possible changes in salivary gland proteomes in response to fluctuations in sex hormone levels. This study aimed to examine the effects of chronic exposure to testosterone on salivary gland remodeling, particularly focusing on proteomic adaptations. Therefore, male Wistar rats were implanted with subcutaneous testosterone-releasing devices at 14 weeks of age. Their submandibular glands were histologically and molecularly analyzed 47 weeks later. The results underscored a significant increase in gland mass after testosterone exposure, further supported by histologic evidence of granular duct enlargement. Despite increased circulating sex hormones, there was no detectable shift in the tissue levels of estrogen alpha and androgen receptors. GeLC-MS/MS and subsequent bioinformatics identified 308 proteins in the submandibular glands, 12 of which were modulated by testosterone. Of note was the pronounced upregulation of Klk3 and the downregulation of Klk6 and Klk7 after testosterone exposure. Protein–protein interaction analysis with the androgen receptor suggests that Klk3 is a potential target of androgenic signaling, paralleling previous findings in the prostate. This exploratory analysis sheds light on the response of salivary glands to testosterone exposure, providing proteome-level insights into the associated weight and histological changes.

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Section: Discussionmentioning

confidence: 99%

Long-Term Exposure to Supraphysiological Levels of Testosterone Impacts Rat Submandibular Gland Proteome

Valente-Santos,

Vitorino,

Sousa-Mendes

et al. 2023

IJMS

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“…Only one human protease, kallikrein-3, has a comparable substrate specificity as M pro for cleavage on the C-terminal side of glutamine. Because kallikrein-3 is a serine protease expressed solely in the prostate gland, 25 inhibitors affecting the cysteine protease M pro are unlikely to target it, and if they do, inhibition will be restricted to the prostate gland.…”

Section: Introductionmentioning

confidence: 99%

Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure–Activity Relationships, Antiviral Activity, and X-ray Structure Determination

et al. 2022

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The main protease (M pro , 3CL pro ) of SARS-CoV-2 is an attractive target in coronaviruses because of its crucial involvement in viral replication and transcription. Here, we report on the design, synthesis, and structure–activity relationships of novel small-molecule thioesters as SARS-CoV-2 M pro inhibitors. Compounds 3w and 3x exhibited excellent SARS-CoV-2 M pro inhibition with k inac / K i of 58,700 M –1 s –1 ( K i = 0.0141 μM) and 27,200 M –1 s –1 ( K i = 0.0332 μM), respectively. In Calu-3 and Vero76 cells, compounds 3h , 3i, 3l , 3r , 3v , 3w , and 3x displayed antiviral activity in the nanomolar range without host cell toxicity. Co-crystallization of 3w and 3af with SARS-CoV-2 M pro was accomplished, and the X-ray structures showed covalent binding with the catalytic Cys145 residue of the protease. The potent SARS-CoV-2 Mpro inhibitors also inhibited the M pro of other beta-coronaviruses, including SARS-CoV-1 and MERS-CoV, indicating that they might be useful to treat a broader range of coronaviral infections.

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Identifying Candidate Biomarkers for Pleomorphic Adenoma: A Case–Control Study

Morrison

Jackson-Boeters

Khan

et al. 2018

Head and Neck Pathol

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Pleomorphic adenoma (PA) is the most common benign salivary gland tumor. Kallikrein-related peptidases have been identified as biomarkers in many human tumors and may influence tumor behavior. We investigated KLK1-15 messenger ribonucleic acid and proteins in PA specimens to determine a KLK expression profile for this tumor. Fresh frozen PA tissue specimens (n = 26) and matched controls were subjected to quantitative real-time reverse transcription polymerase chain reaction to detect KLK1-15 mRNA. Expression of KLK1, KLK12, KLK13, and KLK8 proteins were then evaluated via immunostaining techniques. Statistical analyses were performed with the level of significance set at P < .05. We observed downregulation of KLK1, KLK12, and KLK13 mRNA expression, and immunostaining studies revealed downregulation of the corresponding proteins. Histologic evidence of capsular perforation was associated with increased KLK1 protein expression. Tumor size was not associated with capsular invasion and/or perforation. This study is the first to detail a KLK expression profile for PA at both the transcriptional level and the protein level. Future work is required to develop clinical applications of these findings.

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Human Kallikrein 3 (prostate-specific antigen) and Human Kallikrein 5 Expression in Salivary Gland Tumors

Cited by 5 publications

References 29 publications

Long-Term Exposure to Supraphysiological Levels of Testosterone Impacts Rat Submandibular Gland Proteome

Long-Term Exposure to Supraphysiological Levels of Testosterone Impacts Rat Submandibular Gland Proteome

Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure–Activity Relationships, Antiviral Activity, and X-ray Structure Determination

Identifying Candidate Biomarkers for Pleomorphic Adenoma: A Case–Control Study

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