2006
DOI: 10.1074/jbc.m508603200
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G-protein-coupled OX1 Orexin/hcrtr-1 Hypocretin Receptors Induce Caspase-dependent and -independent Cell Death through p38 Mitogen-/Stress-activated Protein Kinase

Abstract: We have investigated the signaling of OX 1 receptors to cell death using Chinese hamster ovary cells as a model system. OX 1 receptor stimulation with orexin-A caused a delayed cell death independently of cytosolic Ca 2؉ elevation. The classical mitogen-activated protein kinase (MAPK) pathways, ERK and p38, were strongly activated by orexin-A. p38 was essential for induction of cell death, whereas the ERK pathway appeared protective. A pathway often implicated in the p38-mediated cell death, activation of p53,… Show more

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Cited by 76 publications
(79 citation statements)
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“…targets of the MAPK (pMAPK) and PI3K (PDK1) signaling pathways. pMAPK and PDK1 levels were both reduced in the olfactory bulbs with no effect of pMAPK signaling pathway on the diencephalon and brainstem, which are regulators of appetite and arousal However, significantly increased levels of PDK1 measured in the diencephalon and brainstem were consistent with two other studies [17,18]. In cell culture, HC increased levels of both pMAPK and PDK1 dose and time-dependently.…”
Section: Discussionsupporting
confidence: 85%
See 1 more Smart Citation
“…targets of the MAPK (pMAPK) and PI3K (PDK1) signaling pathways. pMAPK and PDK1 levels were both reduced in the olfactory bulbs with no effect of pMAPK signaling pathway on the diencephalon and brainstem, which are regulators of appetite and arousal However, significantly increased levels of PDK1 measured in the diencephalon and brainstem were consistent with two other studies [17,18]. In cell culture, HC increased levels of both pMAPK and PDK1 dose and time-dependently.…”
Section: Discussionsupporting
confidence: 85%
“…Rats in this study were given IN HC and their locomotor activity and appetite were monitored for 24 h. Rats were also given radiolabeled HC at two different doses to determine whether delivery may be dose-dependent. In an effort to determine the mechanism of action, two proteins known to be affected by HC, mitogen-activated protein kinase (MAPK; which is activated) and phosphoinositide-dependent kinase-1 (PDK1; which has increased phosphorylation) [17,18], were assessed by Western blot in the brains after delivery of IN HC. The data demonstrate that IN HC reaches the brain in a dose-dependent manner, affects short-term locomotor activity and appetite, and affects both the MAPK and PDK1 pathways.…”
Section: Introductionmentioning
confidence: 99%
“…Ten micrometer BrdU (Sigma Aldrich, St. Louis, MO) was added to cells on glass and nanorods (Ammoun et al 2006). After 20 h of incubation, cells were fixed with 4% paraformaldehyde for 20 min and washed several times with PBS.…”
Section: -Bromo-2-deoxyuridine (Brdu) Stainingmentioning
confidence: 99%
“…Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (Calbiochem) assay as described before (25,26). In control experiments, staurosporine was used to activate caspase-3 and induce cell death (25).…”
Section: Methodsmentioning
confidence: 99%