Role of oxidative stress in intermittent hypoxia‐induced immediate early gene activation in rat PC12 cells

Yuan, Guoxiang; Adhikary, Gautam; McCormick, Andrew; Holcroft, John. J.; Kumar, Ganesh K.; Prabhakar, Nanduri R.

doi:10.1113/jphysiol.2003.058503

Cited by 130 publications

(140 citation statements)

References 35 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…It is known that hypoxia, as well as reoxygenation, can induce excessive ROS generation, resulting from the univalent reduction of molecular oxygen to O 2 • − by electrons that leak from the mitochondrial electron transport chain, mainly from complexes I and III [13,32]. The repetitive situation of short-term severe hypoxia followed by short-term reoxygenation causes a disturbance of intracellular pro-oxidant/antioxidant homeostasis, which is manifested in the intensification of lipid peroxidation [11,14,33]. The enhanced LPO in mitochondria leads to the loss of mitochondrial membrane fluidity, membrane ionic permeability, including proton permeability, which uncouples oxidative phosphorylation, as well as activity of membrane -bound enzymes [12].…”

Section: Discussionmentioning

confidence: 99%

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Gonchar

2008

Open Life Sciences

View full text Add to dashboard Cite

Abstract:The purpose of this study was to compare the influence of two regimes of intermittent hypoxia (IH) [repetitive 5 cycles of 5 min hypoxia (7% O 2 or 12% O 2 in N 2 ) followed by 15 min normoxia, daily for three weeks] on oxidative stress protective systems in liver mitochondria. To estimate the effectiveness of hypoxia adaptation at the early and late preconditioning period, we exposed rats to acute 6-h immobilization at the 1 st and 45 th days after cessation of IH. We showed that severity of hypoxic episodes during IH might initiate different adaptive programs. Moderate hypoxia during IH prevents mitochondrial glutathione pool depletion induced by immobilization stress, maintains GSH-redox cycle via activation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, NADP + -dependent isocitrate dehydrogenase, and increases Mn-SOD activity. Such regimen of hypoxic preconditioning caused the decrease of mitochondrial superoxide anion generation as well as of basal and stimulated in vitro lipid peroxidation and this protective effect remained for 45 days under renormoxic conditions. Hypoxic adaptation in a more severe regimen exerted beneficial effects on the mitochondrial antioxidant defense system only at its later phase.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Gonchar

2008

Open Life Sciences

View full text Add to dashboard Cite

show abstract

“…One candidate mechanism for unique suppression of phosphatase activity by intermittent, but not sustained, hypoxia is differential ROS formation. Intermittent hypoxia increases superoxide anion formation relative to sustained hypoxia in PC12 cells (Yuan et al, 2004), and ROSs are known to exert powerful influences on the activity of potentially relevant protein kinases and protein phosphatases (Klann and Thiels, 1999). Furthermore, ROSs are necessary for several forms of neural plasticity (Klann, 1998;Knapp and Klann, 2002), including pLTF (MacFarlane and .…”

Section: Protein Phosphatases and Phrenic Ltfmentioning

confidence: 99%

“…Indeed, multiple protein kinases and phosphatases are hypoxia sensitive (Seta et al, 2001(Seta et al, , 2002Truttmann et al, 2004;Liu et al, 2005), although the effects of the hypoxia pattern on protein kinase/phosphatase activity are not known. One possibility is that intermittent and sustained hypoxia differentially regulate protein kinase/phosphatase activity by differences in the generation of reactive oxygen species (ROSs) (Yuan et al, 2004). ROSs regulate the activity of both protein kinases and phosphatases (Klann and Thiels, 1999;Prabhakar and Kumar, 2004) and are necessary for pLTF expression (MacFarlane and Mitchell, 2006).…”

Section: Introductionmentioning

confidence: 99%

Okadaic Acid-Sensitive Protein Phosphatases Constrain Phrenic Long-Term Facilitation after Sustained Hypoxia

Wilkerson¹,

Satriotomo²,

Baker-Herman³

et al. 2008

J. Neurosci.

View full text Add to dashboard Cite

Phrenic long-term facilitation (pLTF) is a serotonin-dependent form of pattern-sensitive respiratory plasticity induced by intermittent hypoxia (IH), but not sustained hypoxia (SH). The mechanism(s) underlying pLTF pattern sensitivity are unknown. SH and IH may differentially regulate serine/threonine protein phosphatase activity, thereby inhibiting relevant protein phosphatases uniquely during IH and conferring pattern sensitivity to pLTF. We hypothesized that spinal protein phosphatase inhibition would relieve this braking action of protein phosphatases, thereby revealing pLTF after SH. Anesthetized rats received intrathecal (C4) okadaic acid (25 nM) before SH (25 min, 11% O 2 ). Unlike (vehicle) control rats, SH induced a significant pLTF in okadaic acid-treated rats that was indistinguishable from rats exposed to IH (three 5 min episodes, 11% O 2 ). IH and SH with okadaic acid may elicit pLTF by similar, serotonin-dependent mechanisms, because intravenous methysergide blocks pLTF in rats receiving IH or okadaic acid plus SH. Okadaic acid did not alter IH-induced pLTF. In summary, pattern sensitivity in pLTF may reflect differential regulation of okadaic acid-sensitive serine/threonine phosphatases; presumably, these phosphatases are less active during/after IH versus SH. The specific okadaic acid-sensitive phosphatase(s) constraining pLTF and their spatiotemporal dynamics during and/or after IH and SH remain to be determined.

show abstract

Section: Figmentioning

confidence: 99%

“…It is well established that hypoxia elevates TH mRNA levels primarily via the transcription factor, activator protein-1 (AP-1) (Semenza, 2000b;Yuan et al, 2004). Evidence indicates that the signaling pathway for AP-1 involves cell depolarization, Ca 2 + -entry, and the immediate early gene, c-fos (Yuan et al, 2004). Our finding that a cocktail of inflammatory cytokines elevate TH levels are consistent with the recent demonstration that IL-1b, acting via IL-1 receptors on type I cells, evokes depolarization and increased [Ca2 + ] I (Shu et al, 2007;Fan et al, 2009).…”

Section: Figmentioning

confidence: 99%

Sustained Exposure to Cytokines and Hypoxia Enhances Excitability of Oxygen-Sensitive Type I Cells in Rat Carotid Body: Correlation with the Expression of HIF-1α Protein and Adrenomedullin

Liu

He²,

Dinger³

et al. 2013

High Altitude Medicine & Biology

View full text Add to dashboard Cite

Liu, X., L. He, B. Dinger, L. Stensaas, and S. Fidone. Sustained exposure to cytokines and hypoxia enhances excitability of oxygen-sensitive type I cells in rat carotid body: Correlation with the expression of HIF-1a protein and adrenomedullin. High Alt Med Biol 14:53-60, 2013.-Recent studies in our laboratory demonstrated that chronic hypoxia (CH) induces a localized inflammatory response in rat carotid body that is characterized by macrophage invasion and increased expression of inflammatory cytokines. Moreover, CH-induced increased hypoxic sensitivity is blocked by concurrent treatment with the common anti-inflammatory drugs, ibuprofen and dexamethasone. The present study examines the hypothesis that selected cytokines enhance the excitability of oxygen-sensitive type I cells in the carotid body, and that downstream effects of cytokines involve upregulation of the transcription factor, hypoxia inducible factor-1a (HIF-1a). Cultured type I cells were exposed for 24 h to hypoxia and/or a cocktail of cytokines consisting of interleukin-1b, interleukin-6, and tumor necrosis factor-a. Subsequent evaluation of hypoxia-evoked intracellular Ca 2 + -responses showed that previous exposure to cytokines plus hypoxia resulted in a 110% ( p < 0.001) increase in cell excitability, whereas exposure to cytokines or hypoxia alone elicited smaller increases of 22% (not significant) and 35% ( p < 0.01), respectively. These changes were correlated with increased immunostaining for HIF-1a in similarly treated type I cells, where exposure to cytokines plus hypoxia promoted the nuclear translocation of the transcription factor. Moreover, treatment with cytokines and/or hypoxia elevated the expression of the HIF-1-regulated gene, adrenomedullin. These in vitro results are supported by studies which show that elevated type I cell sensitivity following in vivo CH is blocked by concurrent treatment with ibuprofen. The data suggest that CH-induced adaptation in arterial chemoreceptors may in part be mediated by cytokine/hypoxia-induced upregulation of HIF-1a, and consequent enhanced expression of specific hypoxia-sensitive genes in type I cells.

show abstract

Role of oxidative stress in intermittent hypoxia‐induced immediate early gene activation in rat PC12 cells

Cited by 130 publications

References 35 publications

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Okadaic Acid-Sensitive Protein Phosphatases Constrain Phrenic Long-Term Facilitation after Sustained Hypoxia

Sustained Exposure to Cytokines and Hypoxia Enhances Excitability of Oxygen-Sensitive Type I Cells in Rat Carotid Body: Correlation with the Expression of HIF-1α Protein and Adrenomedullin

Contact Info

Product

Resources

About