Hypoxia-Inducible Factor 1-α-AA-Modified Bone Marrow Stem Cells Protect PC12 Cells from Hypoxia-Induced Apoptosis, Partially Through VEGF/PI3K/Akt/FoxO1 Pathway

Zhong, Qian; Zhou, Yanfang; Ye, Wei‐Biao; Cai, Tuo; Zhang, Xiuquan; Deng, David Y.B.

doi:10.1089/scd.2011.0604

Cited by 39 publications

(33 citation statements)

References 54 publications

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“…We examined FoxO1 and FoxO3a expression, and found a significant increase in transcripts and non‐significant increase in proteins, in response to hypoxia. This accords with reports that hypoxia increases FoxO1 expression in cardiomyocytes and bone marrow stem cells . We then investigated effects of hypoxia on FoxO shuttling.…”

Section: Discussionsupporting

confidence: 87%

AMPK and FoxO1 regulate catalase expression in hypoxic pulmonary arterial smooth muscle

Awad

Nolette

Hinton

et al. 2013

Pediatric Pulmonology

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Background: Hypoxia and reactive oxygen species (ROS) including H 2 O 2 play major roles in triggering and progression of pulmonary vascular remodeling in persistent pulmonary hypertension. Catalase (CAT), the major endogenous enzyme scavenging H 2 O 2 , is regulated in a tissue-and context-specific manner. Objective: To investigate mechanisms by which hypoxia and H 2 O 2 regulate catalase expression, and the role of AMPK-FoxO pathway, in neonatal porcine pulmonary artery smooth muscle (PASMC). Design/Methods: PASMC were grown in hypoxia (10% O 2 ) or normoxia (21% O 2 ) for 72 hr. We measured catalase activity and lipid peroxidation; CAT, FoxO1, and FoxO3a expression by qPCR; protein contents of CAT, FoxOs, p-AMPK, p-AKT, p-JNK, p-ERK1/2 in whole lysates, and FoxOs in nuclear extracts, by immunoblot; and FoxO-1 nuclear localization by immunocytochemistry, quantified by laser scanning cytometry. Results: Hypoxia upregulated CAT transcription, content and activity, by increasing CAT transcription factors FoxO1 and FoxO3a mRNA, and promoting nuclear translocation of FoxO1. However, lipid peroxidation increased in hypoxic PASMC. Among candidate FoxO regulatory kinases, hypoxia activated AMPK, and decreased p-Akt and ERK1/2. AMPK activation increased FoxO1 (total and nuclear) and CAT, while AMPK inhibition inhibited FoxO1 and CAT, but not FoxO3a. Exogenous H 2 O 2 decreased p-AMPK and increased p-AKT in hypoxic PASMC. This decreased active FoxO1, and reduced mRNA and protein content of CAT. Hypoxic induction of CAT, AKT inhibition (LY294002), or addition of PEG-catalase partly ameliorated the H 2 O 2 -mediated loss of nuclear FoxO1. Conclusions: Hypoxia induces catalase expression, though this adaptation is insufficient to protect PASMC from hypoxia-induced lipid peroxidation. This occurs via hypoxic activation of AMPK, which promotes nuclear FoxO1 and thus catalase expression. Exogenous ROS may downregulate cellular antioxidant defenses; H 2 O 2 activates survival factor Akt, decreasing nuclear FoxO1 and thus catalase.

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Section: Discussionsupporting

confidence: 87%

AMPK and FoxO1 regulate catalase expression in hypoxic pulmonary arterial smooth muscle

Awad

Nolette

Hinton

et al. 2013

Pediatric Pulmonology

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“…The mechanism of the added VEGF that can promote HDPCs proliferation and survive cells from HEMA exposure may involve signal transduction through receptor tyrosine kinases, vascular endothelial growth factor receptor 2 (VEGF-R2), and lead to cell proliferation by either activation of the mitogen-activated protein kinases or MAPK cascade via Raf stimulation or PLC (phospholipase C)-γ. Activation of PI3K (phosphatidylinositol 3-kinase) leads to activation of PKB (protein kinase B) and the cell survival process (7,17). VEGF can also survive cells from hypoxic conditions via the PI3K/Akt/FoxO1 pathway (8). VEGF induces expression of the anti-apoptotic proteins Bcl-2 in vascular endothelial cells (18) and in leukemic cells (19).…”

Section: Discussionmentioning

confidence: 99%

“…Another interesting property of VEGF is helping cells survive from stress or hazardous conditions. There have been some studies reporting that VEGF played a role in survival of serum-starved endothelial cells (6,7), as well as survival of these cells in hypoxic conditions (8). A previous study has also revealed that VEGF expression was upregulated in mouse odontoblast-like cells (MDPC-23) exposed to 2-hydroxyethyl methacrylate (HEMA) (9).…”

Section: Introductionmentioning

confidence: 99%

Effect of recombinant vascular endothelial growth factor and translationally controlled tumor protein on 2‑hydroxyethyl methacrylate‑treated pulp cells

2018

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Vascular endothelial growth factor (VEGF)-A is a potential signaling protein that may promote angiogenesis. VEGF also helps cells survive in stressfull or hazardous conditions. The present study aimed to compare the effect of VEGF with translationally controlled tumor protein (TCTP), an anti‑apoptotic protein in human dental pulp cells (HDPCs), following exposure to 2‑hydroxyethyl methacrylate (HEMA), which is a major residual monomer from resin restorative dental materials. Cell viability, alkaline phosphatase (ALP) activity, mineralization and gene expressions for odontogenic and osteogenic differentiation markers of HDPCs were investigated, following exposure to HEMA and in combination with TCTP and VEGF. The results revealed that TCTP at 1 ng/ml and VEGF at 10 ng/ml significantly promoted the proliferation of HDPCs (P<0.05). TCTP (1 ng/ml) and VEGF (10 ng/ml) maintained the cell viability of 4 mM HEMA‑treated cells at the same percentage as the control. However, cells treated with HEMA+TCTP+VEGF had a lower cell viability than the groups treated with HEMA and TCTP or VEGF alone. TCTP and VEGF promoted cell proliferation, ALP activity and mineralization, and upregulated of DSPP, DMP‑1, BMP‑2, and ALP mRNA expression compared with the control. Furthermore, the HEMA+TCTP and HEMA+VEGF groups had significantly higher percentages of calcium deposition than HEMA‑treated cells (P<0.001). HEMA was cytotoxic to HDPCs, reduced ALP activity and caused the significant downregulation of odontogenic and osteogenic gene expressions (P<0.05). It was concluded that VEGF and TCTP promoted pulp cell growth and the survival of HEMA‑treated cells without synergistic effects. TCTP was required in lower concentrations for these effects. VEGF and TCTP enhanced cell differentiation and mineralization.

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“…Previous studies have demonstrated that the VEGF/ RTK/PI3K/AKT pathway plays a key role in regulating migration, angiogenesis, proliferation and survival (12,13). Downregulation of eNOS increases the sensitivity of Ca 2+ for apoptosis induced by the mitochondria.…”

Section: Signaling Pathwaymentioning

confidence: 99%

Signaling network of OSW-1-induced apoptosis and necroptosis in hepatocellular carcinoma

Jin¹,

Jin²,

Qian³

et al. 2013

Molecular Medicine Reports

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The compound 3β, 16β, 17α-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-β-D-xylopyranosyl)-(1→3)-(2-O-acetyl-α-L-arabinopyranoside (OSW-1) is a member of the cholestane saponin family that was created in the bulbs of Ornithogalum saudersiae. OSW-1 has previously been shown as cytotoxic against numerous types of malignant cells, however, its antitumoral mechanisms remain unclear. The present study aimed to examine the potential changes in the gene expression of a hepatocellular carcinoma (HCC) cell line (Hep3B) incubated with OSW-1 in vitro. The results showed that OSW-1 inhibited tumors through invasiveness, angiogenesis, cell polarity and cell adhesion (as shown by Roche NimbleGen gene expression analysis), in addition to inducing apoptosis through the mitochondrial pathway. This affected the expression of a number of core genes in a number of signaling pathways, including WNT, MAPK, VEGF and P53. To the best of our knowledge, the present study is the first to report that OSW-1, as a molecular compound, induces necroptotic death in hepatocellular carcinoma (HCC).

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Hypoxia-Inducible Factor 1-α-AA-Modified Bone Marrow Stem Cells Protect PC12 Cells from Hypoxia-Induced Apoptosis, Partially Through VEGF/PI3K/Akt/FoxO1 Pathway

Cited by 39 publications

References 54 publications

AMPK and FoxO1 regulate catalase expression in hypoxic pulmonary arterial smooth muscle

AMPK and FoxO1 regulate catalase expression in hypoxic pulmonary arterial smooth muscle

Effect of recombinant vascular endothelial growth factor and translationally controlled tumor protein on 2‑hydroxyethyl methacrylate‑treated pulp cells

Signaling network of OSW-1-induced apoptosis and necroptosis in hepatocellular carcinoma

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