N-Acetylcysteine Partially Reverses Oxidative Stress and Apoptosis Exacerbated by Mg-Deficiency Culturing Conditions in Primary Cultures of Rat and Human Hepatocytes

Martin, Hélène; Abadie, Catherine; Heyd, Bruno; Mantion, Georges; Richert, Lysiane; Berthelot, Alain

doi:10.1080/07315724.2006.10719547

Cited by 16 publications

(9 citation statements)

References 47 publications

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“…1-3). Several studies have reported alterations in cell physiology during magnesium deficiency, but exposure times ranged from hours to days, resulting in detection of acute responses to (typically severe) reductions in magnesium levels (19)(20)(21)(22)(23)(24). Recently, Maier and colleagues have shown the development of senescence features in endothelial cell cultures maintained in low magnesium in just 3-5 days (60).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies on the effects of acute and severe magnesium deficiency on cells in culture have demonstrated reduced oxidative stress defense, cell cycle progression, culture growth, and cellular viability (13,(19)(20)(21)(22)(23)(24)60), whereas the expression of protooncogenes (e.g., c-fos, c-jun) and activation of transcription factors (e.g., NF-B) were increased (25). Few studies have investigated the cellular consequences of long-term and moderate magnesium deficiency in normal human cells.…”

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confidence: 99%

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Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts

Killilea

Ames

2008

Proc. Natl. Acad. Sci. U.S.A.

110

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Magnesium inadequacy affects more than half of the U.S. population and is associated with increased risk for many age-related diseases, yet the underlying mechanisms are unknown. Altered cellular physiology has been demonstrated after acute exposure to severe magnesium deficiency, but few reports have addressed the consequences of long-term exposure to moderate magnesium deficiency in human cells. Therefore, IMR-90 human fibroblasts were continuously cultured in magnesium-deficient conditions to determine the long-term effects on the cells. These fibroblasts did not demonstrate differences in cellular viability or plating efficiency but did exhibit a decreased replicative lifespan in populations cultured in magnesium-deficient compared with standard media conditions, both at ambient (20% O 2) and physiological (5% O 2) oxygen tension. The growth rates for immortalized IMR-90 fibroblasts were not affected under the same conditions. IMR-90 fibroblast populations cultured in magnesium-deficient conditions had increased senescence-associated ␤-galactosidase activity and increased p16 INK4a and p21 WAF1 protein expression compared with cultures from standard media conditions. Telomere attrition was also accelerated in cell populations from magnesium-deficient cultures. Thus, the long-term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate agerelated disease.oxygen tension ͉ telomeres ͉ tumor suppressor M agnesium is an essential micronutrient required for an extensive range of metabolic, regulatory, and structural activities. It is predominantly obtained from diet by eating green leafy vegetables and unprocessed grains (1). The typical U.S. diet has drifted away from these food sources in favor of more refined and often nutrient-poor food options, thus magnesium inadequacy has become quite common (2). Intake estimates generated by national surveys including the National Health and Nutrition Examination Survey (NHANES) have predominantly indicated that more than half of the U.S. population has magnesium intakes below the Estimated Average Requirement (EAR), a measure of population adequacy that is 2 SD below the Recommended Daily Allowance (3). Moreover, the incidence and severity of magnesium inadequacy is even greater in at-risk groups, including children, the poor, and the elderly (4, 5).Despite growing appreciation of the prevalence of magnesium inadequacy, essentially no immediate clinical symptoms are known, due in part to the lack of robust biomarkers of magnesium status in vivo. However, there is a sizeable literature on the functional consequences linked with long-term magnesium inadequacy. Epidemiological data have associated increased risk of several agingrelated diseases with chronic magnesium inadequacy, including cardiovascular disease, hypertension, diabetes, osteoporosis, and some cancers (1, 6-8). Numerous animal studies on magnesium inadequacy...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts

Killilea

Ames

2008

Proc. Natl. Acad. Sci. U.S.A.

110

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“…MgD promoted apoptosis in rat hepatocyte primary culture, which was accompanied by an accumulation of malondialdehyde and a decreased GSH concentration [46]. N-acetylcysteine partially attenuated the apoptosis of human and rat hepatocytes induced by low extracellular Mg concentrations, but surprisingly, also increased both caspase-3 activity and lipid peroxidation in hepatocytes exposed to physiological Mg concentrations [47]. Two hours after exposure to low Mg, human umbilical vein endothelial cells (HUVEC) were more sensitive to the oxidant action of H 2 O 2 and demonstrated an increased level of the DNA damage marker 8-hydroxy-deoxyguanine compared to controls cultured in physiologic concentrations of Mg [48].…”

Section: Oxidative Stress and Magnesium Deficiencymentioning

confidence: 99%

Magnesium deficiency and oxidative stress: an update

Желтова¹,

Kharitonova²,

Iezhitsa³

et al. 2016

BioMed

164

102

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Magnesium deficiency (MgD) has been shown to impact numerous biological processes at the cellular and molecular levels. In the present review, we discuss the relationship between MgD and oxidative stress (OS). MgD is accompanied by increased levels of OS markers such as lipid, protein and DNA oxidative modification products. Additionally, a relationship was detected between MgD and a weakened antioxidant defence. Different mechanisms associated with MgD are involved in the development and maintenance of OS. These mechanisms include systemic reactions such as inflammation and endothelial dysfunction, as well as changes at the cellular level, such as mitochondrial dysfunction and excessive fatty acid production.

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“…However, poor data demonstrate the ability of H 2 O 2 and NAC to exert their pro-and anti-oxidant action in hepatoma cell lines. Furthermore, the window within which H 2 O 2 and NAC are capable to promote/inhibit both apoptosis and cell proliferation in this in vitro model of hepatic cells is still unknown (28)(29)(30).…”

Section: Proliferative and Apoptotic Response Was Dose-related In Hepmentioning

confidence: 99%

Glutathionylation of p65NF-κB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants

Alisi

Piemonte²,

Pastore³

et al. 2009

Int J Mol Med

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Abstract.Oxidative stress influences a variety of regulatory proteins, including nuclear factor-κB (NF-κB). NF-κB is critical for maintaining the proliferation/apoptosis balance in hepatocytes. In this study we investigated the causal links between glutathione, NF-κB and hepatocyte damage. HepG2 and 3B cells were exposed to different doses of H 2 O 2 or N-acetylcysteine (NAC) and the proliferation/apoptosis rate, glutathione forms, and p65NF-κB glutathionylation and activity were analysed. Our results demonstrate that H 2 O 2 stopped proliferative response at low doses, but induced apoptosis only at high doses. In contrast, NAC exerted, proportionally to its concentration, a dual role simultaneously increasing both proliferation and apoptosis. Interestingly, the levels of proteinbound glutathione were increased by H 2 O 2 and decreased by NAC. Moreover, the antibody recognizing the glutathionylated proteins co-precipitated and -localized with the cytoplasmic inactive form of p65NF-κB in H 2 O 2 -and NAC-treated cells, even when, in 1 mM NAC-treated cells, a part of p65 was glutathione-free and localized into the nucleus. Apoptotic cells were characterised principally by a cytoskeletal staining of glutathionylation and retention of NF-κB in the cytoplasmic region; whereas in proliferating cells, glutathionylated proteins were concentrated into the perinuclear region and p65NF-κB was traslocated into the nucleus. While cytoplasmic NF-κB retention correlated well with an increased apoptotic rate, a greater expression of this protein was observed in association with the NAC-dependent. In conclusion, our findings suggest that glutathionylation inhibits NF-κB activity causing reduced hepatocyte survival, which is common in several liver diseases.

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N-Acetylcysteine Partially Reverses Oxidative Stress and Apoptosis Exacerbated by Mg-Deficiency Culturing Conditions in Primary Cultures of Rat and Human Hepatocytes

Cited by 16 publications

References 47 publications

Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts

Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts

Magnesium deficiency and oxidative stress: an update

Glutathionylation of p65NF-κB correlates with proliferating/apoptotic hepatoma cells exposed to pro- and anti-oxidants

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