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Global gene expression analysis reveals a link between NDRG1 and vesicle transport.

ABSTRACT: N-myc downstream-regulated gene 1 (NDRG1) is induced by cellular stress such as hypoxia and DNA damage, and in humans, germ line mutations cause Charcot-Marie-Tooth disease. However, the cellular roles of NDRG1 are not fully understood. Previously, NDRG1 was shown to mediate doxorubicin resistance under hypoxia, suggesting a role for NDRG1 in cell survival under these conditions. We found decreased apoptosis in doxorubicin-treated cells expressing NDRG1 shRNAs under normoxia, demonstrating a requirement for NDRG1 in apoptosis in breast epithelial cells under normal oxygen pressure. Also, different cellular stress regimens, such as hypoxia and doxorubicin treatment, induced NDRG1 through different stress signalling pathways. We further compared expression profiles in human breast epithelial cells ectopically over-expressing NDRG1 with cells expressing NDRG1 shRNAs in order to identify biological pathways where NDRG1 is involved. The results suggest that NDRG1 may have roles connected to vesicle transport.

SUBMITTER: Askautrud HA

PROVIDER: S-EPMC3909102 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Global gene expression analysis reveals a link between NDRG1 and vesicle transport.

Askautrud Hanne A HA Gjernes Elisabet E Gunnes Gjermund G Sletten Marit M Ross Douglas T DT Børresen-Dale Anne Lise AL Iversen Nina N Tranulis Michael A MA Frengen Eirik E

PloS one 20140131 1

N-myc downstream-regulated gene 1 (NDRG1) is induced by cellular stress such as hypoxia and DNA damage, and in humans, germ line mutations cause Charcot-Marie-Tooth disease. However, the cellular roles of NDRG1 are not fully understood. Previously, NDRG1 was shown to mediate doxorubicin resistance under hypoxia, suggesting a role for NDRG1 in cell survival under these conditions. We found decreased apoptosis in doxorubicin-treated cells expressing NDRG1 shRNAs under normoxia, demonstrating a req ...[more]

PMID: 24498060

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Project description:Glucocorticoid hormones are a popular health indicator for animal populations. We find the relationship between health and glucocorticoids is inconsistent. However, variation in glucocorticoids is prevalent and may characterize populations in decline. We suggest monitoring the variation in glucocorticoids within populations might be more useful than mean glucocorticoid levels. Abstract Glucocorticoids are a popular tool for monitoring health of animal populations because they can increase with environmental stressors and can indicate chronic stress. However, individual responses to stressors create variation in the glucocorticoid–fitness relationship within populations. The inconsistency in this relationship calls into question the widespread use of glucocorticoids in conservation. We investigated the sources of variation in the glucocorticoid–fitness relationship by conducting a meta-analysis across a diverse set of species exposed to conservation-relevant stressors. We first quantified the extent to which studies inferred population health from glucocorticoids without first validating the glucocorticoid–fitness relationship in their own populations. We also tested whether population-level information like life history stage, sex and species longevity influenced the relationship between glucocorticoids and fitness. Finally, we tested for a universally consistent relationship between glucocorticoids and fitness across studies. We found more than half of peer-reviewed studies published between 2008 and 2022 inferred population health solely based on glucocorticoid levels. While life history stage explained some variation in the relationship between glucocorticoids and fitness, we found no consistent relationship between them. Much of the variation in the relationship could be the result of idiosyncratic characteristics of declining populations, such as unstable demographic structure, that coincided with large amounts of variation in glucocorticoid production. We suggest that conservation biologists capitalize on this variation in glucocorticoid production by declining populations by using the variance in glucocorticoid production as an early warning for declines in population health.

Dataset Information

Global gene expression analysis reveals a link between NDRG1 and vesicle transport.

Publications

Global gene expression analysis reveals a link between NDRG1 and vesicle transport.

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