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Exosomal secretion ...
Exosomal secretion of death bullets: a new way of apoptotic escape?
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Trokovic, N. (author)
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Pollanen, R. (author)
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Porola, P. (author)
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Stegaev, V. (author)
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Hetzel, U. (author)
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- Tivesten, Åsa, 1969 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Engdahl, Cecilia, 1983 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Carlsten, Hans, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Forsblad d'Elia, Helena, 1961 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet
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- Fagman, Johan Bourghardt, 1980 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Lagerquist, Marie (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Konttinen, Y. T. (author)
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(creator_code:org_t)
- American Physiological Society, 2012
- 2012
- English.
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In: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 303:8
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- Trokovic N, Pollanen R, Porola P, Stegaev V, Hetzel U, Tivesten A, Engdahl C, Carlsten H, Forsblad-D'Elia H, Fagman JB, Lagerquist M, Konttinen YT. Exosomal secretion of death bullets: a new way of apoptotic escape? Am J Physiol Endocrinol Metab 303: E1015-E1024, 2012. First published August 12, 2012; doi: 10.1152/ajpendo.00139.2012.-Ovariectomy/estrogen deficiency causes selective apoptosis of the serous epithelial cells of the submandibular glands (SMG) in female mice. Because such apoptosis does not occur in healthy, estrogen-deficient male mice, it was hypothesized that dihydrotestosterone (DHT) protects epithelial SMG cells against apoptosis. The antiapoptotic effect of DHT on human epithelial HSG cells exposed to tumor necrosis factor-alpha and cycloheximide was studied. Correspondingly, the proapoptotic effect of androgen deficiency was studied in orchiectomized (ORX) androgen-knockout (ARKO) and wild-type (WT) mice. The health state of the SMG cells was studied with Alcian blue-periodic acid Schiff (AB-PAS) and amylase staining and transmission electron microscopy (TEM). The eventual protective antiapoptotic effect of dehydroepiandrosterone (DHEA) treatment was tested in this model. Apoptosis was assessed using immunohistochemisty of cleaved effector caspase-3 and its activator caspase-8 and the TUNEL assay. To test for the bioavailability, intracrine metabolism and sex steroid effects of DHEA, cystein-rich secretory protein-3 (CRISP-3), and leucine-isoleucine-valine transport system 1 (LIV-1) were used as androgen-and estrogen-regulated biomarkers, respectively. DHT protected HSG cells against induced apoptosis. In mice, androgen deficiency resulted in extensive activation of apoptotic caspase-8/3 cascade in serous epithelial cells. However, in salivary glands, active caspases were not translocated to nuclei but secreted to salivary ducts in exosome-like particles, which are associated with weak AB-PAS and amylase staining of the androgen-deprived cells and reduced number of intracellular secretory granules. DHEA treatment suppressed induction of proapoptotic caspases and almost normalized mucins and amylase and ultramophology of the serous epithelial cells in WT ORX but not ARKO ORX mice. According to the CRISP-3 and LIV-1 markers, DHEA probably exerted its effects via intracrine conversion to DHT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- androgens
- apoptosis
- caspase
- submandibular gland
- serous
- resembling sjogrens-syndrome
- human salivary-glands
- androgen receptor
- autoimmune exocrinopathy
- submandibular glands
- deficient mice
- cell
- caspase-3
- dehydroepiandrosterone
- activation
Publication and Content Type
- ref (subject category)
- art (subject category)
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Trokovic, N.
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Pollanen, R.
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Porola, P.
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Stegaev, V.
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Hetzel, U.
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Tivesten, Åsa, 1 ...
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Engdahl, Cecilia ...
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Carlsten, Hans, ...
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Forsblad d'Elia, ...
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Fagman, Johan Bo ...
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Lagerquist, Mari ...
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Konttinen, Y. T.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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American Journal ...
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University of Gothenburg
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Umeå University