Responding to Hypoxia: Lessons From a Model Cell Line

Seta, Karen A.; Spicer, Zachary; Yuan, Yong; Lü, Gang; Millhorn, David E.

doi:10.1126/scisignal.1462002re11

Cited by 38 publications

(51 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, these cells respond even to relatively small changes in oxygen tension. Finally, pheochromocytomas arise from the neuroendocrine medullar cells of the adrenal gland, which is involved in the systemic response to oxygen (24). Here we show that the level of basal (normoxic) as well as hypoxia-induced HIF-2␣ in PC12 cells is diminished by the presence of growth signals.…”

mentioning

confidence: 66%

Down-regulation of Hypoxia-inducible Factor-2 in PC12 Cells by Nerve Growth Factor Stimulation

Naranjo‐Suarez¹,

Castellanos²,

Álvarez-Tejado

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cellular responses to low oxygen tension are mediated, at least in part, by the activation of the hypoxiainducible factors (HIFs). In the presence of oxygen, specific HIF residues become hydroxylated by the action of a recently described group of dioxygenases. These posttranslational modifications target HIF for proteosomal degradation and prevent its transcriptional activity. Despite these detailed studies, little is known about the regulation of HIF by stimuli other than hypoxia. Here we report that, in rat pheochromocytoma PC12 cells, nerve growth factor (

show abstract

mentioning

confidence: 66%

Down-regulation of Hypoxia-inducible Factor-2 in PC12 Cells by Nerve Growth Factor Stimulation

Naranjo‐Suarez¹,

Castellanos²,

Álvarez-Tejado

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Depletion of adenosine triphosphate (ATP) results in either growth arrest or apoptosis, depending on the cell types (12)(13)(14)(15). Many of these responses are mediated by the transcription factor HIF-1 (16), which activates the expression of genes involved in growth arrest, such as the tumor suppressor p53, as well as the CDKIs p21 and p27 (17). Several studies indicate that hypoxia-induced growth arrest is associated with a decrease cyclin-CDK complexes and an increase in CDKI p27, leading to hypophosphorylation of pRb (18,19).…”

mentioning

confidence: 99%

Hypoxia Inhibits Myogenic Differentiation through Accelerated MyoD Degradation

Carlo

Mori

Martelli

et al. 2004

Journal of Biological Chemistry

121

150

View full text Add to dashboard Cite

Cells undergo a variety of biological responses when placed in hypoxic conditions, including alterations in metabolic state and growth rate. Here we investigated the effect of hypoxia on the ability of myogenic cells to differentiate in culture. Exposure of myoblasts to hypoxia strongly inhibited multinucleated myotube formation and the expression of differentiation markers. We showed that hypoxia reversibly inhibited MyoD, Myf5, and myogenin expression. One key step in skeletal muscle differentiation involves the up-regulation of the cell cycle-dependent kinase inhibitors p21 and p27 as well as the product of the retinoblastoma gene (pRb). Myoblasts cultured under hypoxic conditions in differentiation medium failed to up-regulate both p21 and pRb despite the G 1 cell cycle arrest, as evidenced by p27 accumulation and pRb hypophosphorylation. Hypoxia-dependent inhibition of differentiation was associated with MyoD degradation by the ubiquitin-proteasome pathway. MyoD overexpression in C2C12 myoblasts overrode the differentiation block imposed by hypoxic conditions. Thus, hypoxia by inducing MyoD degradation blocked accumulation of early myogenic differentiation markers such as myogenin and p21 and pRb, preventing both permanent cell cycle withdraw and terminal differentiation. Our study revealed a novel anti-differentiation effect exerted by hypoxia in myogenic cells and identified MyoD degradation as a relevant target of hypoxia.

show abstract

“…One of the proteins activated by increased expression of HIF-1alpha is VEGF, a regulator, among other things, of angiogenesis. Several studies have found that overexpression of this protein is an adverse prognostic factor that correlates to the presence of distant metastases or more advanced stages [21]. In fact, this was the only variable remaining in the regression model in our study and, therefore, the protein (end of the VHL-HIF-1alpha pathway) could be a prognostic biomarker for ccRCC.…”

Section: Discussionmentioning

confidence: 60%

Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis

Serrano-Oviedo

Giménez-Bachs

Nam-Cha

et al. 2017

Urologic Oncology: Seminars and Original Investigations

View full text Add to dashboard Cite

Objectives: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters.Material and methods: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables.A bivariate and multivariate descriptive logistical regression analysis was performed, using the presence of metastasis at diagnosis as dependent variable.Results: The study identified 13 (26%) VHL mutations related to nuclear grade (P ¼ 0.036). VHL hypermethylation was found in 20% of cases. VHL expression was associated with the presence of mutations (P ¼ 0.013), and the absence of expression was associated with nuclear grade and the presence of metastasis (P o 0.05). HIF-1alpha was negative in only 5 cases. Vascular endothelial growth factor (VEGF) was positive in 31 of 47 cases and was associated with Fuhrman nuclear grade, presence of metastasis, and stage (P o 0.05). ERK5 expression was increased in 58% of cases and associated with the presence of metastasis and more advanced stages (P o 0.05). In the logistic regression analysis, the only variable remaining in the model was VEGF expression (P ¼ 0.014).Conclusions: VEGF has prognostic value in clear cell renal cell carcinoma, and ERK5 may be a new prognostic marker in this type of tumor owing to its relationship with metastasis and more advanced stages. r

show abstract

Responding to Hypoxia: Lessons From a Model Cell Line

Cited by 38 publications

References 160 publications

Down-regulation of Hypoxia-inducible Factor-2 in PC12 Cells by Nerve Growth Factor Stimulation

Down-regulation of Hypoxia-inducible Factor-2 in PC12 Cells by Nerve Growth Factor Stimulation

Hypoxia Inhibits Myogenic Differentiation through Accelerated MyoD Degradation

Implication of VHL, ERK5, and HIF-1alpha in clear cell renal cell carcinoma: Molecular basis

Contact Info

Product

Resources

About