Antioxidant <i>N</i>‐acetyl‐<scp>l</scp>‐cysteine inhibits erythropoietin‐induced differentiation of erythroid progenitors derived from mouse fetal liver

Nagata, Mizuki; Arimitsu, Nagisa; Ito, Takahiro; Sekimizu, Kazuhisa

doi:10.1016/j.cellbi.2006.11.001

Cited by 15 publications

(14 citation statements)

References 27 publications

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“…It has been shown that ROS production induces further ROS generation (57), meaning that the effect of NAC on the outcome measures of the present study may be more pronounced if the infusion is maintained throughout the recovery period and possibly also during the insulin clamp. Additionally, despite our focus on skeletal muscle, our whole body IS findings should be interpreted with caution since the liver also plays an important role in glucose metabolism, which can be affected by NAC (32,44). Finally, although our small sample size may potentially be a limitation, these sample sizes have been used previously in similarly invasive studies, which include several muscle biopsies and hyperinsulinemic euglycemic clamps, across two sessions for each participant (15,45).…”

Section: Discussionmentioning

confidence: 96%

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

Trewin

Lundell²,

Perry

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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produced in skeletal muscle may play a role in potentiating the beneficial responses to exercise; however, the effects of exerciseinduced ROS on insulin action and protein signaling in humans has not been fully elucidated. Seven healthy, recreationally active participants volunteered for this double-blind, randomized, repeated-measures crossover study. Exercise was undertaken with infusion of saline (CON) or the antioxidant N-acetylcysteine (NAC) to attenuate ROS. Participants performed two 1-h cycling exercise sessions 7-14 days apart, 55 min at 65% V O2peak plus 5 min at 85%V O2peak, followed 3 h later by a 2-h hyperinsulinemic euglycemic clamp (40 mIU·min Ϫ1 ·m 2 ) to determine insulin sensitivity. Four muscle biopsies were taken on each trial day, at baseline before NAC infusion (BASE), after exercise (EX), after 3-h recovery (REC), and postinsulin clamp (PI). Exercise, ROS, and insulin action on protein phosphorylation were evaluated with immunoblotting. NAC tended to decrease postexercise markers of the ROS/protein carbonylation ratio by Ϫ13.5% (P ϭ 0.08) and increase the GSH/GSSG ratio twofold vs. CON (P Ͻ 0.05). Insulin sensitivity was reduced (Ϫ5.9%, P Ͻ 0.05) by NAC compared with CON without decreased phosphorylation of Akt or AS160. Whereas p-mTOR was not significantly decreased by NAC after EX or REC, phosphorylation of the downstream protein synthesis target kinase p70S6K was blunted by 48% at PI with NAC compared with CON (P Ͻ 0.05). We conclude that NAC infusion attenuated muscle ROS and postexercise insulin sensitivity independent of Akt signaling. ROS also played a role in normal p70S6K phosphorylation in response to insulin stimulation in human skeletal muscle.

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Section: Discussionmentioning

confidence: 96%

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

Trewin

Lundell²,

Perry

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…Recently, it was shown that EPO production and erythroid differentiation are regulated by RONS, especially H 2 O 2 , which are involved in redox-sensitive signalling pathways through down-regulation of transcription factors [7,24,25]. This means that RONS generation can suppress EPO synthesis whereas antioxidants can stimulate its synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, however, it was recognised that NAC enhances transiently tissue damage and oxidative stress suggesting that NAC may work as a pro-oxidant and deteriorate exercise performance [5,6]. Secondly, NAC was marked as a useful compound to regulate the differentiation of erythroid progenitors [7]. It has been also helpful in increasing the plasma EPO concentration in humans before and during hypoxia [8].…”

mentioning

confidence: 99%

Modulatory effect of N-acetylcysteine on pro-antioxidant status and haematological response in healthy men

et al. 2010

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The aim of this study was to follow up whether the modification of pro-antioxidant status by 8-day oral application of N-acetylcysteine (NAC) in healthy men affects the haematological response, whether there is a direct relationship between antioxidant defences and erythropoietin (EPO) secretion and whether NAC intake enhances exercise performance. Fifteen healthy men were randomly assigned to one of two groups: control or NAC (1,200 mg d(-1) for 8 days prior to and 600 mg on the day of exercise trial). To measure the ergogenic effectiveness of NAC, subjects performed incremental cycle exercise until exhaustion. NAC administration significantly influenced the resting and post-exercise level of glutathione (+31%) as well as the resting activity of glutathione enzymes (glutathione reductase, -22%; glutathione peroxidase, -18%). The oxidative damage markers, i.e., protein carbonylation and lipid peroxidation products (thiobarbituric acid reactive substance) were reduced by NAC by more than 30%. NAC noticeably affected the plasma level of EPO (+26%), haemoglobin (+9%), haematocrit (+9%) and erythrocytes (-6%) at rest and after exercise. The mean corpuscular volume and the mean corpuscular haemoglobin increased by more than 12%. Plasma total thiols increased by 17% and directly correlated with EPO level (r = 0.528, P < 0.05). NAC treatment, contrary to expectations, did not significantly affect exercise performance. Our study has shown that 8-day NAC intake at a daily dose of 1,200 mg favours a pro-antioxidant status and affects haematological indices but does not enhance exercise performance.

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“…Furthermore, it has been suggested that ROS are involved in Epo-mediated erythroid differentiation and that antioxidants could attenuate erythropoiesis (Nagata et al, 2007). However, it has been also reported that hemolysis is directly proportional to LPO and protein oxidation (Vani et al, 2010).…”

Section: Vitamin C and Erythropoiesismentioning

confidence: 99%

Vitamin C Supplementation Does not Improve Hypoxia-Induced Erythropoiesis

Martínez-Bello

Sanchís-Gomar

Martinez‐Bello

et al. 2012

High Altitude Medicine & Biology

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a. Vitamin C Supplementation Does Not Improve Hypoxia-Induced Erythropoiesis. High Alt Med Biol 13:269-274, 2012.-Hypoxia induces reactive oxygen species production. Supplements with antioxidant mixtures can compensate for the decline in red cell membrane stability following intermittent hypobaric hypoxia by decreasing protein and lipid oxidation. We aimed to determine whether supplementation with vitamin C is implicated in the regulation of erythropoiesis and in the oxygen-carrying capacity of the blood, and also whether antioxidant supplementation prevents the oxidative stress associated to intermittent hypoxia. Twentyfour male Wistar rats were randomly divided into four experimental groups: normoxia control (n = 6), normoxia + vitamin C (n = 6), hypoxia control (12 h pO 2 12%/12 h pO 2 21%) (n = 6), and hypoxia + vitamin C (n = 6). Animals were supplemented with vitamin C at a dose of 250 mg$kg -1 $day -1 for 21 days. Red blood cell count, hemoglobin, hematocrit, reticulocytes, erythropoietin, and oxidative stress parameters such as malondialdehyde and protein oxidation in plasma were analyzed at two different time points: basal sample (day zero) and final sample (day 21). Similar RBC, Hb, Hct, and Epo increments were observed in both hypoxic groups regardless of the vitamin C supplementation. There was no change on MDA levels after intermittent hypoxic exposure in any experimental group. However, we found an increase in plasma protein oxidation in both hypoxic groups. Vitamin C does not affect erythropoiesis and protein oxidation in rats submitted to intermittent hypoxic exposure.

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Antioxidant N‐acetyl‐l‐cysteine inhibits erythropoietin‐induced differentiation of erythroid progenitors derived from mouse fetal liver

Cited by 15 publications

References 27 publications

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

Modulatory effect of N-acetylcysteine on pro-antioxidant status and haematological response in healthy men

Vitamin C Supplementation Does not Improve Hypoxia-Induced Erythropoiesis

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