Search results for "Secretor"
showing 10 items of 159 documents
Mutant p53 induces Golgi tubulo-vesiculation driving a prometastatic secretome
2020
TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading …
The Effect of a Novel c.820C>T (Arg274Trp) Mutation in the Mitofusin 2 Gene on Fibroblast Metabolism and Clinical Manifestation in a Patient
2017
Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant axonal peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2). Mitofusin 2 is a GTPase protein present in the outer mitochondrial membrane and responsible for regulation of mitochondrial network architecture via the fusion of mitochondria. As that fusion process is known to be strongly dependent on the GTPase activity of mitofusin 2, it is postulated that the MFN2 mutation within the GTPase domain may lead to impaired GTPase activity, and in turn to mitochondrial dysfunction. The work described here has therefore sought to verify the effects of MFN2 mutation within its GTPase domain on mitochondrial and e…
Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.
2020
An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secret…
Psychophysics, flare, and neurosecretory function in human pain models: capsaicin versus electrically evoked pain.
2007
Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are analyzed in respect to patterns and test-retest reliability of pain as well as sensory and neurosecretory changes. In 10 healthy subjects, 2 CAP (50 g) and 2 ES (5 to 30 mA) were applied to the volar forearm. The time period between 2 identical stimulations was about 4 months. Pain ratings, areas of mechanical hyperalgesia, and allodynia were assessed. The intensity of sensory changes was quantified by using quantitative sensory testing. Neurogenic flare was assessed by using laser Doppler imaging. Calcito- nin gene-related peptide (CGRP) release was quantified by dermal microdialysis in combination with an en…
Recovery of immune control over herpes simplex virus type 1 in female victims of intimate partner violence.
2009
Objectives: To assess the course of immune control over Herpes simplex virus type 1 (HSV-1) through three salivary measures: neutralization of HSV-1, levels of specific antibody against HSV-1 (HSV-1-sIgA) and total immunoglobulin A (total sIgA), and to determine the factors that contribute to its recovery or deterioration. Several studies have demonstrated that intimate partner violence (IPV) affects immune responses in women, but none have investigated the impact longitudinally over time. Methods: Women (n = 60), who participated in our previous cross-sectional study (T-1) and who had been either physically/psychologically (n = 22) or psychologically abused (n = 14) by their partners, were…
DNA Hypomethylation and Histone Variant macroH2A1 Synergistically Attenuate Chemotherapy-Induced Senescence to Promote Hepatocellular Carcinoma Progr…
2016
Abstract Aging is a major risk factor for progression of liver diseases to hepatocellular carcinoma (HCC). Cellular senescence contributes to age-related tissue dysfunction, but the epigenetic basis underlying drug-induced senescence remains unclear. macroH2A1, a variant of histone H2A, is a marker of senescence-associated heterochromatic foci that synergizes with DNA methylation to silence tumor-suppressor genes in human fibroblasts. In this study, we investigated the relationship between macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, and liver carcinogenesis. We found that protein levels of both macroH2A1 isoforms were increased in the livers of very elderly rodents and humans, a…
Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
2021
Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of large aggregates in the survival neurons called Lewy bodies, which mainly contain α-synuclein (α-syn). The cause of cell death is not known but could be due to mitochondrial dysfunction, protein homeostasis failure, and alterations in the secretory/endolysosomal/autophagic pathways. Survival nigral neurons overexpress the small GTPase Rab1. This protein is considered a housekeeping Rab that is necessary to support the secretory pathway, the maintenance of the Golgi complex structure, and the regulation of macroau…
Evidence for the plant-specific intercellular transport of the Arabidopsis copper chaperone CCH
2001
Summary Arabidopsis copper chaperone (CCH) belongs to a family of eukaryotic proteins that participates in intracellular copper homeostasis by delivering this metal to the secretory pathway. In this work we show that the CCH protein is mainly located along the vascular bundles of senescing leaves and petioles, as shown by tissue prints and immunohistochemical detection. CCH protein also accumulates in stem sieve elements and is collected in phloem exudates. Accordingly, Arabidopsis CCH is the only member of the metallochaperone family described to function intercellularly to date. Moreover, the CCH protein remains stable when plants are subjected to excess copper that causes a rapid and spe…
Distribution and coexistence of chromogranin A-, serotonin-and pancreastatin-like immunoreactivity in endocrine-like cells of the human anal canal
1992
The comparative distribution and coexistence of chromogranin A (CGA)-, serotonin (5-hydroxytryptamine; 5-HT)- and pancreastatin (PST)-like immunoreactivity in endocrine-like cells of the human anal canal was investigated by light-microscopic immunocytochemistry. The largest population of colorectal endocrine-like cells consisted of CGA-immunoreactive (ir) cells, followed by the 5-HT-ir and PST-ir cell population. In the anal transitional zone (ATZ), CGA- and 5-HT-immunoreactivity was equally distributed; ir-PST was confined to a smaller endocrine-like cell population. In the squamous zone and the perianal skin, Merkel cells in the basal layer of the epidermis and hair follicles exhibited ir…
Stx5 is a novel interactor of VLDL-R to affect its intracellular trafficking and processing
2012
We identified syntaxin 5 (Stx5), a protein involved in intracellular vesicle trafficking, as a novel interaction partner of the very low density lipoprotein (VLDL)-receptor (VLDL-R), a member of the LDL-receptor family. In addition, we investigated the effect of Stx5 on VLDL-R maturation, trafficking and processing. Here, we demonstrated mutual association of both proteins using several in vitro approaches. Furthermore, we detected a special maturation phenotype of VLDL-R resulting from Stx5 overexpression. We found that Stx5 prevented advanced Golgi-maturation of VLDL-R, but did not cause accumulation of the immature protein in ER, ER to Golgi compartments, or cis-Golgi ribbon, the main ex…