Potential Role of IGF-I in Hypoxia Tolerance Using a Rat Hypoxic-Ischemic Model: Activation of Hypoxia-Inducible Factor 1α

Wang, Xinghe; Deng, Jixian; Boyle, David W.; Zhong, Jin; Lee, Wei Hua

doi:10.1203/01.pdr.0000111482.43827.40

Cited by 39 publications

(17 citation statements)

References 47 publications

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“…These findings provide support of our previous study which showed that the levels of IGF-I in the systemic and ocular compartments differ possibly because of the ocular-blood barrier (16). The increase in ocular IGF-1 levels in response to JB1 treatment may be due to increased production of IGF-1 through hypoxia-induced IGF-1 transcriptional activation (17). Alternatively, the effect may be explained by accumulation of IGF-I due to binding of IGF-1R to JB1, thereby preventing IGF-I transport and uptake.…”

Section: Discussionsupporting

confidence: 89%

“…However, longer exposure with JB1x7 had an opposite effect on IGF-1 in the ocular compartment and was not associated with exacerbated neovascularization at P21, as expected. These intriguing findings raise the possibility that a rebound increase in IGF-I levels after exposure to JB1 may have provided protection against oxidative injury and contributed to hypoxia tolerance as previously reported by Wang et al (17). In that context, the JB1x3 dosing regimen was more effective for normalization of retinal IGF-I levels and retinal vascular abnormalities seen with H/H cycling.…”

Section: Discussionsupporting

confidence: 70%

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Biomolecular Effects of Jb1 (an IGF-I Peptide Analog) in a Rat Model of Oxygen-Induced Retinopathy

et al. 2011

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Low-serum IGF-I levels at birth is a risk factor for the development of retinopathy of prematurity in extremely LBW infants. We tested the hypothesis that JB1 (an IGF-I analog) prevents oxygen-induced retinopathy in our rat model. Neonatal rats were exposed to 50% oxygen with brief, clustered, hypoxic (12%) episodes from birth to P14. The pups were treated with s.c. injections of 1) JB1 (1 g/d) on P1, P2, and P3 (JB1x3); 2) JB1 (1 g/d) on alternate days from P1 to P13 (JB1x7); or 3) equivalent volume saline. Control littermates were raised in room air (RA) with all conditions identical except for inspired O 2 . Groups were analyzed after hyperoxia/hypoxia (H/H) cycling at P14 or allowed to recover in RA until P21. Systemic and ocular VEGF, soluble VEGFR-1, and IGF-I; retinal vasculature; and gene profile of retinal angiogenesis were assessed. JB1x3 was more effective with associated increases in sVEGFR-1 and decreased retinal pathologies than JB1x7. We conclude that early short-term exposure to systemic JB1 treatment normalizes retinal abnormalities seen with H/H cycling, an effect that may involve sVEGFR-1. (Pediatr Res 69: 135-141, 2011)

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 70%

Biomolecular Effects of Jb1 (an IGF-I Peptide Analog) in a Rat Model of Oxygen-Induced Retinopathy

et al. 2011

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“…The increase in HIF-1␣ was detectable in both the ipsi-and contralateral hemisphere and also after hypoxia only. These findings are not surprising inasmuch as hypoxia is the crucial signal for increased expression of HIF-1␣ (23,24). Simultaneously with increased HIF-1␣ protein expression, we observed a sharp decrease in P-Akt.…”

Section: Discussionsupporting

confidence: 63%

Bilateral Molecular Changes in a Neonatal Rat Model of Unilateral Hypoxic-Ischemic Brain Damage

et al. 2006

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Perinatal hypoxia ischemia (HI) is a frequent cause of neonatal brain injury. This study aimed at describing molecular changes during the first 48 h after exposure of the neonatal rat brain to HI. Twelve-day-old rats were subjected to unilateral carotid artery occlusion and 90 min of 8% O 2 , leading to neuronal damage in the ipsilateral hemisphere only. Phosphorylated-Akt levels were decreased from 0.5 to 6 h post-HI, whereas the level of phosphorylated extracellular signal-related kinases (ERK)1/2 increased during this time frame. Hypoxia-inducible factor (HIF)-1␣ protein increased with a peak at 3 h after HI. mRNA expression for IL-␤ and tumor necrosis factor-␣ and -␤ started to increase at 6 h with a peak at 24 h post-HI. Expression of heat shock protein 70 was increased from 12 h after HI onwards in the ipsilateral hemisphere only. Surprisingly, HI changed the expression of cytokines, HIF1-␣ ,and P-Akt to the same extent in both the ipsi-as well as the contralateral hemisphere, although neuronal damage was unilateral. Exposure of animals to hypoxia without carotid artery occlusion induced similar changes in cytokines, HIF-1␣, and P-Akt. We conclude that during HI, hypoxia is sufficient to regulate multiple molecular mediators that may contribute, but are not sufficient, to induce long-term neuronal damage. A commonly used neonatal rat model to investigate hypoxic-ischemic brain damage is the Vannucci-Rice model. This model implicates unilateral common carotid artery ligation followed by inhalation of 8% O 2 for 1-2 h. This procedure leads to cerebral damage restricted to the hemisphere ipsilateral to the occluded artery (4).Early after induction of cerebral damage, death, and survival, kinase signalling pathways are known to be activated, including the phosphatidyl-inositol 3 kinase/Akt (PI3-K/Akt) and the ERK1/2 pathways. The phosphorylated forms of these kinases have been shown to be up-regulated after HI in vivo as well as in vitro and are thought to be involved in neuronal cell apoptosis (5-7). Activation of the PI3-K/Akt and the ERK1/2 signaling routes enhance translation of the transcription factor HIF-1␣ (8 -10). In addition, reduced cellular oxygen levels increase the stability of HIF-1␣ protein. More than 40 genes containing the promoter sequence for HIF-1␣ have been identified. Most of these genes play a key role in neuroprotective processes such as angiogenesis/vascular remodeling, erythropoiesis, glucose transport, glycolysis, iron transport, and cell proliferation/neuronal survival (11). Increased HIF-1␣ levels therefore regulate adaptation of the cell to a hypoxic environment (12). Another factor induced after HI that has been implicated in both cellular protection and damage, is HSP70. HSP70 is a chaperone molecule, which is induced in cells after stress such as heat, stretch, or hypoxia (13,14). Intracellular HSP70 is thought to protect cells by binding to denatured proteins, thereby preventing further denaturation or degradation of the proteins. In addition, there is evidence that...

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“…Feldser et al (15) demonstrated that insulin, IGF-I, and IGF-2 induce expression of HIF-1α, which is required for expression of genes encoding IGF-2, IGFBP-2 and IGFBP-3. Recent studies further confirmed that IGF-I transcriptional activation by HIF-1α is a metabolic adaptive responses to hypoxia (38); IGF-I stimulates HIF-1α accumulation, HIF-1α nuclear translocation, and HIF-1 activity, resulting in increased VEGF expression (13,16). Given these prior observations, the possible interaction between the HIF-1α P582S polymorphism and the IGF axis observed in this study provides new evidence that the growth hormone/insulin/IGF-axis may play an important role in prostate cancer development and angiogenesis.…”

Section: Discussionmentioning

confidence: 80%

Effect of a HIF-1 Alpha Polymorphism on the Incidence and Prostate Cancer

Bubley¹

2007

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE 01-02-20072. REPORT TYPE Final DATES COVERED Background:The P582S C->T and A588T G->A polymorphisms in the Hypoxia-inducible factor-1α (HIF-1α) gene have been associated with enhanced stability of the protein and androgen-independent prostate cancer (CaP). Methods: We examined the association of these polymorphisms with CaP among 1,072 incident cases and 1,271 controls, and further explored their joint associations with various prediagnostic plasma hormone levels.Results: The A588T polymorphism was too rare to provide meaningful conclusions and the P582S polymorphism was not associated with CaP. We observed a significant interaction of the P582S genotype with insulin-like growth factor binding protein (IGFBP)-3 in modifying CaP risk such that higher IGFBP-3 levels (>= versus

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Potential Role of IGF-I in Hypoxia Tolerance Using a Rat Hypoxic-Ischemic Model: Activation of Hypoxia-Inducible Factor 1α

Cited by 39 publications

References 47 publications

Biomolecular Effects of Jb1 (an IGF-I Peptide Analog) in a Rat Model of Oxygen-Induced Retinopathy

Biomolecular Effects of Jb1 (an IGF-I Peptide Analog) in a Rat Model of Oxygen-Induced Retinopathy

Bilateral Molecular Changes in a Neonatal Rat Model of Unilateral Hypoxic-Ischemic Brain Damage

Effect of a HIF-1 Alpha Polymorphism on the Incidence and Prostate Cancer

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