Elucidation of brefeldin A-induced ER and Golgi stress responses in Neuro2a cells

ABSTRACT Two genes involved in protein secretion, encoding the Rab protein YPT1/YPTA and the general fusion factor NSFI/NSFA, were characterized from two filamentous fungi, Trichoderma reesei and Aspergillus niger var. awamori. The isolated genes showed a high level of conservation with their Saccharomyces cerevisiae and mammalian counterparts, and T. reesei ypt1 was shown to complement yeast Ypt1p depletion. The transcriptional regulation of the T. reesei ypt1, nsf1, and sar1 genes, involved in protein trafficking, was studied with mycelia treated with the folding inhibitor dithiothreitol (DTT) and with brefeldin A, which inhibits membrane traffic between the endoplasmic reticulum and Golgi complex. The well-known inducer of the yeast and T. reesei unfolded protein response (UPR), DTT, induced the nsf1 gene and the protein disulfide isomerase gene, pdi1, in both of the experiments, and sar1 mRNA increased in only one experiment under strong UPR induction. The ypt1 mRNA did not show a clear increase during DTT treatment. Brefeldin A strongly induced pdi1 and all of the intracellular trafficking genes studied. These results suggest the possibility that the whole secretory pathway of T. reesei could be induced at the transcriptional level by stress responses caused by protein accumulation in the secretory pathway.

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Smac mimetic suppresses tunicamycin-induced apoptosis via resolution of ER stress

Cell Death and Disease ◽

10.1038/s41419-019-1381-z ◽

2019 ◽

Vol 10 (3) ◽

Cited By ~ 5

Author(s):

Behnaz Ahangarian Abhari ◽

Nicole McCarthy ◽

Marie Le Berre ◽

Michelle Kilcoyne ◽

Lokesh Joshi ◽

...

Keyword(s):

Er Stress ◽

Stress Responses ◽

Transcriptional Activation ◽

Brefeldin A ◽

Nuclear Factor Κb ◽

Protein Glycosylation ◽

Dominant Negative ◽

Smac Mimetics ◽

Smac Mimetic ◽

Induced Apoptosis

Abstract Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation. In contrast, BV6 does not rescue cell death induced by other typical ER stressors (i.e., thapsigargin (TG), dithiothreitol, brefeldin A, bortezomib, or 2-deoxyglucose). The protection from TM-triggered apoptosis is found for structurally different Smac mimetics and for genetic knockdown of cellular IAP (cIAP) proteins in several cancer types, underlining the broader relevance. Interestingly, lectin microarray profiling reveals that BV6 counteracts TM-imposed inhibition of protein glycosylation. BV6 consistently abolishes TM-stimulated accumulation of ER stress markers such as glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and reduces protein kinase RNA-like ER kinase (PERK) phosphorylation and X box-binding protein 1 (XBP1) splicing upon TM treatment. BV6-stimulated activation of nuclear factor-κB (NF-κB) contributes to the resolution of ER stress, since NF-κB inhibition by overexpression of dominant-negative IκBα superrepressor counteracts the suppression of TM-stimulated transcriptional activation of CHOP and GRP78 by BV6. Thus, our study is the first to show that Smac mimetic protects from TM-triggered apoptosis by resolving the UPR and ER stress. This provides new insights into the regulation of cellular stress responses by Smac mimetics.

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Effect of brefeldin A (BFA) on the unique surface coat of pulmonary intravascular macrophages (PIMs) of sheep: Ultrastructural and cytochemical study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100145935 ◽

1993 ◽

Vol 51 ◽

pp. 18-19

Author(s):

Baljit Singh

Keyword(s):

Brefeldin A ◽

Ultrastructural Feature ◽

Surface Coat ◽

Anterograde Transport ◽

Cytochemical Study ◽

Active Involvement ◽

Electron Lucent ◽

Pulmonary Intravascular Macrophages ◽

Unique Surface

The PIM of sheep, calf, goat and horse has a characteristic ultrastructural feature in the form of a unique, heparin sensitive, globular surface coat present around the plasma membrane with an intervening electron lucent space of 32-40 nm. We previously showed the active involvement of this surface coat in the phagocytosis of tracer material like monastral blue and cationized ferritin. The surface coat is capable of reconstitution in vivo following disruption with heparin. The present study was aimed to investigate whether PIM is the source of surface coat or not. In the recent years the BFA has been extensively used to understand the secretory pathways in the cells because of its ability to cause a rapid and reversible block to the anterograde transport of proteins from the endoplasmic reticulum to the Golgi.Sheep (n=6) were weighed, their plasma volume was calculated indirectly and based on which a sufficient single intravenous dose of BFA was given so as to reach a concentration of 4-5 microgram/ml of plasma.

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Emotions and health: The impact of emotions, emotions regulation, music, and acculturation on health

Zeitschrift für Gesundheitspsychologie ◽

10.1026/0943-8149.16.3.112 ◽

2008 ◽

Vol 16 (3) ◽

pp. 112-115 ◽

Cited By ~ 1

Author(s):

Stephan Bongard ◽

Volker Hodapp ◽

Sonja Rohrmann

Keyword(s):

Stress Responses ◽

Physiological Stress ◽

Anger Expression ◽

Domain Specific ◽

Cardiovascular Stress ◽

Expression Behavior ◽

Cardio Vascular ◽

And Coping ◽

Relationship Of ◽

The Impact

Abstract. Our unit investigates the relationship of emotional processes (experience, expression, and coping), their physiological correlates and possible health outcomes. We study domain specific anger expression behavior and associated cardio-vascular loads and found e.g. that particularly an open anger expression at work is associated with greater blood pressure. Furthermore, we demonstrated that women may be predisposed for the development of certain mental disorders because of their higher disgust sensitivity. We also pointed out that the suppression of negative emotions leads to increased physiological stress responses which results in a higher risk for cardiovascular diseases. We could show that relaxation as well as music activity like singing in a choir causes increases in the local immune parameter immunoglobuline A. Finally, we are investigating connections between migrants’ strategy of acculturation and health and found e.g. elevated cardiovascular stress responses in migrants when they where highly adapted to the German culture.

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Childbirth and Posttraumatic Stress Responses

European Journal of Psychological Assessment ◽

10.1027/1015-5759.22.4.259 ◽

2006 ◽

Vol 22 (4) ◽

pp. 259-267 ◽

Cited By ~ 40

Author(s):

Eelco Olde ◽

Rolf J. Kleber ◽

Onno van der Hart ◽

Victor J.M. Pop

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Stress Responses ◽

Rating Scales ◽

Rating Scale ◽

Stress Disorder ◽

Traumatic Experience ◽

Event Scale ◽

Self Rating ◽

The Impact

Childbirth has been identified as a possible traumatic experience, leading to traumatic stress responses and even to the development of posttraumatic stress disorder (PTSD). The current study investigated the psychometric properties of the Dutch version of the Impact of Event Scale-Revised (IES-R) in a group of women who recently gave birth (N = 435). In addition, a comparison was made between the original IES and the IES-R. The scale showed high internal consistency (α = 0.88). Using confirmatory factor analysis no support was found for a three-factor structure of an intrusion, an avoidance, and a hyperarousal factor. Goodness of fit was only reasonable, even after fitting one intrusion item on the hyperarousal scale. The IES-R correlated significantly with scores on depression and anxiety self-rating scales, as well as with scores on a self-rating scale of posttraumatic stress disorder. Although the IES-R can be used for studying posttraumatic stress reactions in women who recently gave birth, the original IES proved to be a better instrument compared to the IES-R. It is concluded that adding the hyperarousal scale to the IES-R did not make the scale stronger.

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