Intracellular alkalosis during hypoxia in newborn mouse brain in the presence of systemic acidosis: a phosphorus magnetic resonance spectroscopic study

Mitsufuji, Nobuto; Yoshioka, Hiroshi; Tominaga, Masashi; Okano, Shinji; Nishiki, Tetsuo; Sawada, Tadashi

doi:10.1016/0387-7604(95)00053-e

Cited by 14 publications

(13 citation statements)

References 25 publications

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“…Bickler, 1992). Only a few studies have observed hypoxic alkalization in cancer cells (for review, see Webb et al, 2011) and certain mammalian cells, in keeping with our results (Mitsufuji et al, 1995). Such an alkalization of the intracellular pH during anoxia could well be an adaptive strategy to avoid apoptosis, known to be associated with intracellular acidification (Lagadic-Gossmann et al, 2004;Matsuyama et al, 2000).…”

Section: Responses To Anoxia and Subsequent Reoxygenationsupporting

confidence: 71%

“…Other authors (e.g. Mitsufuji et al, 1995) suggested that the increasing pH values might be attributed to the activation of the Na + /H + antiporter during hypoxia. As the Na + gradient across the cellular membrane is maintained by the Na + /K + -dependent ATPase, the driving force for the proton export by the Na + /H + antiporter is an energy (ATP)-dependent process.…”

Section: Responses To Anoxia and Subsequent Reoxygenationmentioning

confidence: 99%

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The physiological response of the marine platyhelminthMacrostomum lignanoto different environmental oxygen concentrations

Rivera‐Ingraham

Bickmeyer

Abele

2013

Journal of Experimental Biology

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SUMMARYThe respiration rate of meiofauna is difficult to measure, and the response to variations in the environmental oxygen concentration has so far been mainly addressed through behavioral investigation. We investigated the effect of different oxygen concentrations on the physiology of the marine platyhelminth Macrostomum lignano. Respiration was measured using batches of 20 animals in a glass microtiter plate equipped with optical oxygen sensor spots. At higher oxygen saturations (>12kPa), the animals showed a clear oxyconforming behavior. However, below this value, the flatworms kept respiration rates constant at 0.064±0.001nmol O 2 l ) -showed increased ROS formation following anoxia-reoxygenation treatment. Animals exposed to hyperoxic, normoxic and anoxic treatments displayed no significant differences in O 2 • -formation, whereas mitochondrial ROS formation as detected by C-H 2 DFFDA was higher after hyperoxic exposure and lowest under near-anoxia conditions compared with the normoxic control group. Macrostomum lignano seems to be a species that is tolerant of a wide range of oxygen concentrations (being able to maintain aerobic metabolism from extremely low P O2 up to hyperoxic conditions), which is an essential prerequisite for successfully dealing with the drastic environmental oxygen variations that occur within intertidal sediments. Supplementary material available online at

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Section: Responses To Anoxia and Subsequent Reoxygenationsupporting

confidence: 71%

Section: Responses To Anoxia and Subsequent Reoxygenationmentioning

confidence: 99%

The physiological response of the marine platyhelminthMacrostomum lignanoto different environmental oxygen concentrations

Rivera‐Ingraham

Bickmeyer

Abele

2013

Journal of Experimental Biology

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“…Yao and Haddad, 2004). Depending on the experiment conditions and the preparation, hypoxia can cause a fall (Melzian et al, 1996; Roberts, Jr. et al, 2000; von Hanwehr et al, 1986), or a rise (Cowan and Martin, 1995; Mitsufuji et al, 1995; Yao et al, 2001), or a fall followed by a rise (Diarra et al, 1999; Melzian et al, 1996; Sheldon and Church, 2002) of pH i in the CNS.…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic continuous hypoxia on the expression of SLC4A8 (NDCBE) in neonatal versus adult mouse brain

2008

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Na-coupled HCO3 transporters (NCBTs) play important roles in brain pH regulation. One NCBT, the Na-driven Cl-HCO3 exchanger (SLC4A8 or NDCBE), appears to be the major regulator of intracellular pH (pHi), at least in some hippocampal pyramidal neurons. NDCBE is widely expressed throughout the central nervous system in rodent brain. In a previous study, it has been demonstrated that CCH decreases the abundance of NBCn1 and NBCn2 proteins in four regions of the mouse brain: cerebral cortex (CX), subcortex (SCX), cerebellum (CB), and hippocampus (HC). Here we report the effect of CCH (11% O2) on the expression of NDCBE protein in mouse brain. Neonates (beginning at age P2) or adult mice (beginning at P90) were subjected to either normoxia or CCH for durations of 14 or 28 days. Membrane-protein levels were assessed by western blotting using our polyclonal antibody directed against NDCBE. In neonates, CCH significantly decreased NDCBE expression in HC after 14 days and SCX after 28 days, but had no significant effect for other combinations of region/duration. In adults, however, CCH significantly decreased (by 20–50%) the expression of NDCBE in all four brain regions, both with 14 and 28 days’ duration. Thus, the mouse brain exhibits marked developmental differences in the response of NDCBE protein expression to CCH. We hypothesize that decreases in adult NDCBE protein levels, which are probably out of proportion to the decreases in other proteins, may be part of an adaptive response that reduces energy consumption and/or stabilizes brain pHi. The smaller or absent responses in the young animals could be related to neonatal hypoxia tolerance.

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“…Similarly, anoxia in hippocampal slices causes a fall in extracellular pH (36). Regarding pH i , at first glance, it appears that acute hypoxia produces variable effects, sometimes a fall in pH i (43,58,69), sometimes a rise (19,44,75), and sometimes a fall followed by a rise (22,43,65). However, it is likely that the intrinsic effect of acute hypoxia on neuronal pH i is reproducible but depends in important ways on species (i.e., rat vs. mouse), cell type (e.g., brainstem vs. hippocampus), preparation (i.e., slices vs. acutely dissociated cells vs. cells in primary culture), temperature (i.e., room temperature vs. 37°C), and especially on the buffer (i.e., HCO 3 Ϫ -free vs. CO 2 /HCO 3 Ϫ ; see Ref.…”

mentioning

confidence: 99%

“…The central nervous system (CNS) also rapidly responds with several metabolic adaptations (3,39,40,44,54,74,78). Over a longer period of time, the acclimation to hypoxemia includes both functional and structural changes in many tissues, including the CNS (for reviews, see Refs.…”

mentioning

confidence: 99%

Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain

Chen¹,

Choi²,

Haddad³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Chen L-M, Choi I, Haddad GG, Boron WF. Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain. Am J Physiol Regul Integr Comp Physiol 293: R2412-R2420, 2007. First published October 10, 2007; doi:10.1152/ajpregu.00497.2007.-In the mammalian CNS, hypoxia causes a wide range of physiological effects, and these effects often depend on the stage of development. Among the effects are alterations in pH homeostasis. Na ϩ -coupled HCO 3 Ϫ transporters can play critical roles in intracellular pH regulation and several, such as NCBE and NBCn1, are expressed abundantly in the central nervous system. In the present study, we examined the effect of chronic continuous hypoxia on the expression of two electroneutral Na-coupled HCO 3 Ϫ transporters, SLC4a7 (NBCn1) and SLC4a10 (NCBE), in mouse brain, the first such study on any acid-base transporter. We placed the mice in normobaric chambers and either maintained normoxia (21% inspired O 2) or imposed continuous chronic hypoxia (11% O2) for a duration of either 14 days or 28 days, starting from ages of either postnatal age 2 days (P2) or P90. We assessed protein abundance by Western blot analysis, loading equal amounts of total protein for each condition. In most cases, hypoxia reduced NBCn1 levels by 20 -50%, and NCBE levels by 15-40% in cerebral cortex, subcortex, cerebellum, and hippocampus, both after 14 and 28 days, and in both pups and adults. We hypothesize that these decreases, which are out of proportion to the expected overall decreases in brain protein levels, may especially be important for reducing energy consumption. electroneutral; bicarbonate transporter; SLC4; central nervous system HYPOXIA, A LOW-OXYGEN LEVEL in tissue, may be either continuous or intermittent. Chronic continuous hypoxia (CCH) may occur during normal events, such as embryonic development and ascent to altitude, and in pathological states, such as pulmonary disease (i.e., decreased O 2 uptake), anemia (i.e., decreased O 2 content in blood), ischemia (i.e., decreased blood flow to tissues), and cancer (i.e., increased O 2 utilization by tissues). Chronic intermittent hypoxia (CIH) occurs during obstructive sleep apnea. Due to its very high energy demands, the mammalian brain is particularly sensitive to hypoxia.Mammals immediately respond to hypoxemia by increasing first alveolar ventilation and then heart rate. The central nervous system (CNS) also rapidly responds with several metabolic adaptations (3,39,40,44,54,74,78). Over a longer period of time, the acclimation to hypoxemia includes both functional and structural changes in many tissues, including the CNS (for reviews, see Refs. 35,39,and 74). Structural changes in response to chronic hypoxia include a decrease in body mass and an increase in capillary density, which in the brain can amount to a doubling over a period of ϳ4 wk (7, 41) (for reviews, see Refs. 39 and 74). The angiogenic response is under the control of hypoxia-inducible factor-1 (for reviews, see Refs. 29, 33, and 64) and an...

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Intracellular alkalosis during hypoxia in newborn mouse brain in the presence of systemic acidosis: a phosphorus magnetic resonance spectroscopic study

Cited by 14 publications

References 25 publications

The physiological response of the marine platyhelminthMacrostomum lignanoto different environmental oxygen concentrations

The physiological response of the marine platyhelminthMacrostomum lignanoto different environmental oxygen concentrations

Effects of chronic continuous hypoxia on the expression of SLC4A8 (NDCBE) in neonatal versus adult mouse brain

Chronic continuous hypoxia decreases the expression of SLC4A7 (NBCn1) and SLC4A10 (NCBE) in mouse brain

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