IGF‐I neuroprotection in the immature brain after hypoxia‐ischemia, involvement of Akt and GSK3β?

Brywe, Katarina G; Mallard, Carina; Gustavsson, Malin; Hedtjärn, Maj; Leverin, Anna-Lena; Wang, Xiaoyang; Blomgren, Klas; Isgaard, Jörgen; Hagberg, Henrik

doi:10.1111/j.1460-9568.2005.03982.x

Cited by 126 publications

(106 citation statements)

References 64 publications

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“…Increased BrdU-labeling in the SVZ following long-term bGH treatment could, therefore, reflect an influence on the stem cell pool via increased cell survival. Although effects on cell survival have been previously demonstrated for both GH (Gustafson et al 1999, Azcoitia et al 2005 and IGF-I , Brywe et al 2005 following injury, the hypothesis of bGH effects on the SVZ stem cells remains speculative, due to a lack of conclusive markers for adult neural stem cells.…”

Section: Proliferation and Cell Survival -Magnitudesmentioning

confidence: 99%

Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

Åberg

Johansson²,

Åberg³

et al. 2009

Journal of Endocrinology

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IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH-and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate. Subsequently, the rats received daily s.c. injections of bGH for either 6 or 28 days respectively. Following 5 days of peripheral bGH administration, the number of bromodeoxyuridine (BrdU)-positive cells was increased in the hippocampus, striatum, parietal cortex, and piriform cortex after 6 and 28 days. In the SVZ, however, BrdU-positive cells increased only after 28 days of bGH treatment. No significant change was observed in the corpus callosum. In the hippocampus, after 28 days of bGH treatment, the number of BrdU/NeuN-positive cells was increased proportionally to increase the number of BrdUpositive cells.3 H-thymidine incorporation in vitro revealed that 24 h of bGH exposure was sufficient to increase cell proliferation in adult hippocampal progenitor cells. This study shows for the first time that 1) peripheral bGH treatment increased the number of newborn cells in the adult brain and 2) bGH exerted a direct proliferative effect on neuronal progenitor cells in vitro.

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Section: Proliferation and Cell Survival -Magnitudesmentioning

confidence: 99%

Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

Åberg

Johansson²,

Åberg³

et al. 2009

Journal of Endocrinology

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“…Pro-apoptotic functions of GSK-3β have been shown in apoptosis by withdrawal of growth factors, [81][82][83] DNA damage, 52,84 mitochondrial toxins, 85 ischemia, 86,87 oxidant stress 88 and other conditions that trigger apoptosis via the mitochondrial pathway. Phosphorylation of 4 GSK-3β substrates (p53, heat shock factor-1 [HSF-1], myeloid cell leukemia sequence-1 [MCL-1], Bax) is involved in the pro-apoptotic functions.…”

Section: Role Of Gsk-3β In Apoptosis Of Cardiomyocytesmentioning

confidence: 99%

GSK-3.BETA., a Therapeutic Target for Cardiomyocyte Protection

Miura

Miki

2009

Circ J

131

112

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lycogen synthase kinase-3β (GSK-3β) is a constitutively active 47-kDa Ser/Thr protein kinase that was purified more than 2 decades ago as a kinase that reduces glycogen synthase activity. However, GSK-3β is now known as a multifunctional kinase having more than 40 substrates, playing roles not only in glycogen metabolism but also cell proliferation, growth and death. [1][2][3] To properly execute its functions, GSK-3β has multiple regulatory mechanisms including phosphorylation at Ser and Tyr residues, complex formation with scaffold proteins, priming of substrates and intracellular translocation. Recently, pathophysiological roles of GSK-3β have also received attention because it is involved in common and serious diseases such as Alzheimer's disease, bipolar mood disorder, cancer and ischemia/reperfusion injury. 1,3 In the cardiovascular system, GSK-3β has major roles in glucose metabolism, 4 cardiomyocyte hypertrophy 5 and cell death. The roles of GSK-3β in hypertrophy have recently been reviewed by Sugden et al 5 , so therefore we have focused on the roles of this protein kinase in myocyte death, particularly that after ischemia/ reperfusion. We first briefly overview mechanisms of ischemia/reperfusion injury and then discuss the contribution of GSK-3β to cardiomyocyte death and manipulation of GSK-3β for myocardial protection. Mechanisms of Cardiomyocyte Necrosis During Ischemia/ReperfusionWhen myocardial blood perfusion is interrupted, for example by occluding the coronary artery, ischemic cardiomyocytes suffer from several critical intracellular events that can lead to cell necrosis and/or prime the cells to reperfusion-induced necrosis. First, intracellular level of highenergy phosphate is reduced due to oxygen deficiency. Although ischemic cardiomyocytes cease contraction within a few minutes after the onset of ischemia, adenosine triphosphate (ATP) consumption continues during ischemia mainly by mitochondrial ATPase for maintenance of mitochondrial membrane potential. 6,7 Anaerobic glycolysis supplies ATP during the early period of ischemia, but it is ultimately halted by inhibition of glyceraldehyde phosphate dehydrogenase due to accumulated H + and NADH. 7,8 Second, intracellular Na + accumulates due to Na + influx via Na + -H + exchangers and Na + channels and due to reduced Na + efflux via the Na + -K + pump. [9][10][11] This Na + overload predisposes ischemic cardiomyocytes to Ca 2+ influx by the Na + -Ca 2+ exchanger. Third, Ca 2+ influx via the Na + -Ca 2+ exchanger, reduced Ca 2+ uptake into the sarcoplasmic reticulum and reduced Ca 2+ efflux via the sarcolemmal Ca 2+ pump induce Ca 2+ overload in ischemic cardiomyocytes. 9-12 However, elevation of intracellular Ca 2+ is modest during ischemia because acidosis inhibits the Na + -Ca 2+ exchanger and cytosolic Ca 2+ is taken up by the mitochondria as long as its membrane potential is maintained by use of ATP. [9][10][11]13 Severely ischemic cardiomyocytes ultimately 'starve to death', although sarcolemmal damage by detergent actions of accumulated...

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“…Apoptotic cell death induced by hypoxia-ischemia was correlated with a decrease of IGF-1 mRNA in the neonatal rat brain [51]. IGF-1 administration reduced hypoxia/ischemia-induced injury to the immature brain of 7-day old rats by approximately 40% [52]. Likewise, IGF-1 protection against cell death and impaired myelination in a neonatal rat model of white matter damage was demonstrated [53].…”

Section: Discussionmentioning

confidence: 90%

“…HIF-1 is an oxygen-regulated transcriptional complex that controls a large number of oxygen-regulated genes. An increase in HIF-1α activity would result in metabolic, angiogenic and apoptotic adaptive responses, contributing to neuroprotection [52,55]. HIF-1α accumulation and HIF-1 target gene activation were triggered by systemic administration of IGF-1 in the adult rat brain [55].…”

Section: Discussionmentioning

confidence: 99%

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

Prévot

Julita²,

Tung

et al. 2009

Pediatr Nephrol

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Acute normocapnic hypoxemia can cause functional renal insufficiency by increasing renal vascular resistance (RVR), leading to renal hypoperfusion and decreased glomerular filtration rate (GFR). Insulin-like growth factor 1 (IGF-1) activity is low in fetuses and newborns and further decreases during hypoxia. IGF-1 administration to humans and adult animals induces preand postglomerular vasodilation, thereby increasing GFR and renal blood flow (RBF). A potential protective effect of IGF-1 on renal function was evaluated in newborn rabbits with hypoxemia-induced renal insufficiency. Renal function and hemodynamic parameters were assessed in 17 anesthetized and mechanically ventilated newborn rabbits. After hypoxemia stabilization, saline solution (time control) or IGF-1 (1 mg/kg) was given as an intravenous (i.v.) bolus, and renal function was determined for six 30-min periods. Normocapnic hypoxemia significantly increased RVR (+16%), leading to decreased GFR (−14%), RBF (−19%) and diuresis (−12%), with an increased filtration fraction (FF). Saline solution resulted in a worsening of parameters affected by hypoxemia. Contrarily, although mean blood pressure decreased slightly but significantly, IGF-1 prevented a further increase in RVR, with subsequent improvement of GFR, RBF and diuresis. FF indicated relative postglomerular vasodilation. Although hypoxemiainduced acute renal failure was not completely prevented, IGF-1 elicited efferent vasodilation, thereby precluding a further decline in renal function.

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IGF‐I neuroprotection in the immature brain after hypoxia‐ischemia, involvement of Akt and GSK3β?

Cited by 126 publications

References 64 publications

Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats

GSK-3.BETA., a Therapeutic Target for Cardiomyocyte Protection

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

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