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Open AccessArticle

Salivary Histatin 1 and 2 Are Targeted to Mitochondria and Endoplasmic Reticulum in Human Cells

1
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
2
Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam (VU), The Netherlands
3
Department of Oral Implantology and ProstPhetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors shared the last authorship.
Cells 2020, 9(4), 795; https://doi.org/10.3390/cells9040795 (registering DOI)
Received: 10 January 2020 / Revised: 20 March 2020 / Accepted: 25 March 2020 / Published: 26 March 2020
Human salivary histatin 1 (Hst1) and Hst2 exhibit a series of cell-activating properties (e.g., promoting adhesion, spreading, migration and metabolic activity of mammalian cells). In contrast, Hst5 shows an anti-fungal property but no cell-activating properties. Previous findings suggest that their uptake and association with subcellular targets may play a determinant role in their functions. In this study, we studied the uptake dynamics and subcellular targets of Hst1, Hst2 and Hst5 in epithelial cells (HO1N1 human buccal carcinoma epithelial cell line). Confocal laser scanning microscopy (CLSM) revealed that fluorescently labeled Hst1 (F-Hst1) was taken up into the intracellular space of epithelial cells. Then, 60 min post-incubation, the total fluorescence of cell-associated F-Hst1, as measured using flow cytometry, was significantly higher compared to those of F-Hst2 and F-Hst5. In contrast, virtually no association occurred using the negative control—scrambled F-Hst1 (F-Hstscr). CLSM images revealed that F-Hst1, 2 and 5 co-localized with mitotrackerTM-labeled mitochondria. In addition, F-Hst1 and F-Hst2 but neither F-Hst5 nor F-Hst1scr co-localized with the ER-trackerTM-labeled endoplasmic reticulum. No co-localization of Hst1, 2 and 5 with lysosomes or the Golgi apparatus was observed. Furthermore, Hst1 and Hst2 but not Hst5 or Hst1scr significantly promoted the metabolic activity of both human epithelial cell lines, HaCaT human keratinocytes and primary human gingival fibroblasts.
Keywords: histatin; uptake; mitochondria; endoplasmic reticulum; oral saliva histatin; uptake; mitochondria; endoplasmic reticulum; oral saliva
MDPI and ACS Style

Ma, D.; Sun, W.; Nazmi, K.; Veerman, E.C.I.; Bikker, F.J.; Jaspers, R.T.; Bolscher, J.G.M.; Wu, G. Salivary Histatin 1 and 2 Are Targeted to Mitochondria and Endoplasmic Reticulum in Human Cells. Cells 2020, 9, 795.

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