Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

Chu, Hannah X; Jones, Nicole M.

doi:10.1007/s11064-015-1641-y

Cited by 25 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HIF-1α would be degraded by proteasomes under normoxic conditions. However, HIF-1α would be transferred into the nucleus and bind to HIF-1β to form HIF-1, which would subsequently initiate or promote transcription of effector genes under hypoxia conditions [29,30]. As the main transcription factor of hypoxia, HIF-1α has been extensively studied in cerebral ischemia, and the neuro-protective effects of HIF-1α have also been elucidated in various studies.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

et al. 2020

View full text Add to dashboard Cite

Nowadays, searching for new therapeutic targets for cerebral stroke treatment are still in urgent need. Our study explored the influences and mechanisms of HIF-1α on OGD/R-evoked injury. OGD/R treatment was conducted on PC12 cells to simulate ischemic injury. CCK-8, flow cytometry and qRT-PCR were conducted to determine the variations of cell viability, apoptosis and gene expression, respectively. Cell transfections were conducted to overexpress HIF-1α and miR-134. Variations of protein levels were evaluated by employing western blot. Results showed that OGD/R treatment induced cell injury through reducing viability, while enhancing apoptosis that was validated by the elevated ratios of C/P-PARP and C/ P-caspase-3. HIF-1α expression was markedly increased by OGD/R treatment. HIF-1α overexpression attenuated OGD/R-evoked injury in PC12 cells and remarkably reversed OGD/R-triggered inhibitory effects on ERK1/2 and JAK1/STAT3 pathways. Besides, miR-134 was also down-regulated by HIF-1α overexpression in PC12 cells. Up-regulation of miR-134 notably counteracted HIF-1α overexpression-triggered neuroprotective impacts on OGD/R-evoked injury and ERK1/2 and JAK1/STAT3 pathways. Our present study reported that HIF-1α overexpression protected PC12 cells against OGD/R-evoked injury via downregulation of miR-134, which making HIF-1α and miR-134 to be promising targets for cerebral stroke therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In the adult human kidney and fetal liver, the release of EPO into the circulation depends upon tissue oxygen levels and transcription of the EPO gene is mediated via hypoxia-inducible factor (HIF)-2α [ 66 ]. In most tissues, including the brain, hypoxia-dependent expression of EPO and the EPOR is regulated principally by HIF-1, an a,b-heterodimeric protein which is activated by a collection of stimulators, such as hypoxia [ 67 , 68 ]. Each member of the HIF family, including HIF-1α, HIF-1β, and HIF-3α, appears to play an important role in the regulation of EPO and EPOR expression to protect against hypoxic cell injury [ 69 ].…”

Section: Expression Of Epo and Epor In The Nervous Systemmentioning

confidence: 99%

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

Cheng

Wang

et al. 2016

IJMS

View full text Add to dashboard Cite

During the past decade, accumulating evidence from both clinical and experimental studies has indicated that erythropoietin may have antidepressant effects. In addition to the kidney and liver, many organs have been identified as secretory tissues for erythropoietin, including the brain. Its receptor is expressed in cerebral and spinal cord neurons, the hypothalamus, hippocampus, neocortex, dorsal root ganglia, nerve axons, and Schwann cells. These findings may highlight new functions for erythropoietin, which was originally considered to play a crucial role in the progress of erythroid differentiation. Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling pathways including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system. This is particularly true for the hippocampus, which is possibly related to learning, memory, neurocognitive deficits and mood alterations. Thus, the influence of erythropoietin on the downstream pathways known to be involved in the treatment of depression makes the erythropoietin-related pathway an attractive target for the development of new therapeutic approaches. Focusing on erythropoietin may help us understand the pathogenic mechanisms of depression and the molecular basis of its treatment.

show abstract

“…HIF-1α is degraded by proteasomes under normoxic conditions. In response to hypoxia, however, HIF-1α is transferred into the nucleus and interacts with the HIF-1β subunit to form HIF-1 to initiate or enhance transcription of effector genes, including BNIP3/BNIP3L, insulin-like growth factor II, and vascular endothelial growth factor (Chu and Jones 2016 ; Xiong et al 2015 ).…”

Section: Introductionmentioning

confidence: 99%

HIF-1α/Beclin1-Mediated Autophagy Is Involved in Neuroprotection Induced by Hypoxic Preconditioning

Tan

et al. 2018

J Mol Neurosci

View full text Add to dashboard Cite

Hypoxic preconditioning (HPC) exerts a protective effect against hypoxic/ischemic brain injury, and one mechanism explaining this effect may involve the upregulation of hypoxia-inducible factor-1 (HIF-1). Autophagy, an endogenous protective mechanism against hypoxic/ischemic injury, is correlated with the activation of the HIF-1α/Beclin1 signaling pathway. Based on previous studies, we hypothesize that the protective role of HPC may involve autophagy occurring via activation of the HIF-1α/Beclin1 signaling pathway. To test this hypothesis, we evaluated the effects of HPC on oxygen-glucose deprivation/reperfusion (OGD/R)-induced apoptosis and autophagy in SH-SY5Y cells. HPC significantly attenuated OGD/R-induced apoptosis, and this effect was suppressed by the autophagy inhibitor 3-methyladenine and mimicked by the autophagy agonist rapamycin. In control SH-SY5Y cells, HPC upregulated the expression of HIF-1α and downstream molecules such as BNIP3 and Beclin1. Additionally, HPC increased the LC3-II/LC3-I ratio and decreased p62 levels. The increase in the LC3-II/LC3-I ratio was inhibited by the HIF-1α inhibitor YC-1 or by Beclin1-short hairpin RNA (shRNA). In OGD/R-treated SH-SY5Y cells, HPC also upregulated the expression levels of HIF-1α, BNIP3, and Beclin1, as well as the LC3-II/LC3-I ratio. Furthermore, YC-1 or Beclin1-shRNA attenuated the HPC-mediated cell viability in OGD/R-treated cells. Taken together, our results demonstrate that HPC protects SH-SY5Y cells against OGD/R via HIF-1α/Beclin1-regulated autophagy.

show abstract

Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic–Ischemic Injury in the Neonatal Rat

Cited by 25 publications

References 32 publications

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

Erythropoietin Pathway: A Potential Target for the Treatment of Depression

HIF-1α/Beclin1-Mediated Autophagy Is Involved in Neuroprotection Induced by Hypoxic Preconditioning

Contact Info

Product

Resources

About