Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P42345 (
mTOR
)
26,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved,
in vitro
, using PC-3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib
in vitro
. Immunofluorescence staining of
microtubule associated protein 1A
/1B-light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment. Western blot analysis was performed to evaluate variations in the levels of LC3, sequestosome-1, extracellular signal regulated kinase 1/2 (ERK1/2),
mammalian target of rapamycin
(
mTOR
), p70 ribosomal protein S6 kinase (p70S6K) and cleaved caspase-3 proteins. The present study revealed that sunitinib treatment inhibited cell growth and triggered autophagy in a dose-dependent manner in both cell lines. In addition, sunitinib activated ERK1/2 and inhibited
mTOR
/p70S6K signaling. Sunitinib-induced autophagy was notably reversed by ERK1/2 kinase inhibitor, U0126. Furthermore, inhibition of sunitinib-induced autophagy by 3-methyladenine enhanced apoptosis and exhibited improved cell viability, which indicated that sunitinib induces not only apoptosis but also autophagic cell death in prostate cancer cell lines. These results may lead to an improved understanding of the mechanism of sunitinib's cytotoxic action and may provide evidence that combined sunitinib autophagy-regulating treatment may be of benefit to anti-prostate cancer therapy.
...
PMID:Antitumor effect of sunitinib in human prostate cancer cells functions via autophagy. 2841 68
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with self-renewing properties; thus, transplanting functionally enhanced MSCs might be a promising strategy for cell therapy against ischemic diseases. However, extensive oxidative damage in ischemic tissue affects the cell fate of transplanted MSCs, eventually resulting in cell damage and autophagic cell death. Oleuropein (OLP) is a bioactive compound isolated from olives and olive oil that harbors antioxidant properties. This study aimed to investigate the potential cytoprotective effects of OLP against oxidative stress and autophagic cell death in MSCs. We found that short-term priming with OLP attenuated H
2
O
2
-induced apoptosis by regulating the pro-apoptotic marker Bax and the anti-apoptotic markers Bcl-2 and Mcl-1. Notably, OLP inhibits H
2
O
2
-induced autophagic cell death by modulating autophagy-related death signals, including
mTOR
(
mammalian target of rapamycin
), ULK1 (unc-51 like autophagy activating kinase 1), Beclin-1, AMPK (AMP-activated protein kinase), and LC3 (
microtubule-associated protein 1a
/1b-light chain 3). Our data suggest that OLP might reduce H
2
O
2
-induced autophagy and cell apoptosis in MSCs by regulating both the AMPK-ULK axis and the Bcl-2-Mcl-1 axis. Consequently, short-term cell priming with OLP might enhance the therapeutic effect of MSCs against ischemic vascular diseases, which provides an important potential improvement for emerging therapeutic strategies.
...
PMID:Oleuropein attenuates hydrogen peroxide-induced autophagic cell death in human adipose-derived stem cells. 2960 75
Anorexia nervosa is an eating disorder often associated with intestinal disorders. To explore the underlying mechanisms of these disorders, the colonic proteome was evaluated during activity-based anorexia. Female C57Bl/6 mice were randomized into three groups: Control, Limited Food Access (LFA) and Activity-Based Anorexia (ABA). LFA and ABA mice had a progressive limited access to food but only ABA mice had access to an activity wheel. On colonic mucosal protein extracts, a 2D PAGE-based comparative proteomic analysis was then performed and differentially expressed proteins were identified by LC-ESI-MS/MS. Twenty-seven nonredundant proteins that were differentially expressed between Control, LFA, and ABA groups were identified. ABA mice exhibited alteration of several mitochondrial proteins involved in energy metabolism such as dihydrolipoyl dehydrogenase and 3-mercaptopyruvate sulfurtransferase. In addition, a downregulation of
mammalian target of rapamycin
(
mTOR
) pathway was observed leading, on the one hand, to the inhibition of protein synthesis, evaluated by puromycin incorporation and mediated by the increased phosphorylation of eukaryotic elongation factor 2, and on the other hand, to the activation of autophagy, assessed by the increase of the marker of autophagy, form LC3-phosphatidylethanolamine conjugate/Cytosolic form of
Microtubule-associated protein 1A
/1B light chain 3 (LC3II/LC3I) ratio. Colonic mucosal proteome is altered during ABA suggesting a downregulation of energy metabolism. A decrease of protein synthesis and an activation of autophagy were also observed mediated by
mTOR
pathway.
...
PMID:Colonic Mucosal Proteome Signature Reveals Reduced Energy Metabolism and Protein Synthesis but Activated Autophagy during Anorexia-Induced Malnutrition in Mice. 2993 6
