Cardiac changes in apoptosis, inflammation, oxidative stress, and nitric oxide system induced by prenatal and postnatal zinc deficiency in male and female rats

Juriol, Lorena; Gobetto, María Natalia; Abregú, Facundo Mendes Garrido; Dasso, Maximiliano; Pineda, Gonzalo Ezequiel; Güttlein, Leandro N.; Carranza, Andrea; Podhajcer, Osvaldo L.; Toblli, Jorge Eduardo; Elesgaray, Rosana; Arranz, Cristina; Tomat, Analia Lorena

doi:10.1007/s00394-016-1343-5

Cited by 19 publications

(14 citation statements)

References 66 publications

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“…Although excessive NO is cytotoxic to cancer cells [27], physiological level of intracellular NO is essential for cell survival and proliferation [60]. Recently, Juriol et al demonstrate that zinc deficiency activates apoptotic and inflammatory processes with decreased nitric oxide synthase activity in cardiac tissue of rats [53]. In the present study, we found that TPEN induces apoptosis of NB4 APL cells by downregulating intracellular NO signaling.…”

Section: Discussionsupporting

confidence: 63%

“…Hashemi et al demonstrate that TPEN-triggered apoptosis in MCF-7 and MDA-MB468 breast cancer cells can be reversed by the ROS scavenger NAC [47]. Juriol et al demonstrate that zinc deficiency induces NADPH oxidase-dependent superoxide anion production and increases antioxidant enzymes activity in cardiac tissue of male rats [53]. Recently, Mendivilperez et al demonstrate that TPEN induces apoptosis of acute lymphoblastic leukemia (ALL) cells independently of its zinc chelating activity.…”

Section: Discussionmentioning

confidence: 99%

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Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zhu

Wang

Zhou

et al. 2017

Cell Physiol Biochem

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Background/Aims: The effects of zinc signaling on proliferation or apoptosis of leukemia cells remain elusive. In the present study, we used N, N, N’, N’-tetrakis-(2-pyridylmethyl)-ethylene-diamine (TPEN), a membrane-permeable zinc chelator, to evaluate the effect of zinc depletion on survival and apoptosis of NB4 acute promyelocytic leukemia (APL) cells. Methods: The pro-apoptotic effects of TPEN on NB4 cells were examined by flow cytometry, and observed using an optical microscope. Intracellular labile zinc, nitric oxide (NO) or reactive oxygen species (ROS) changes caused by TPEN were measured by flow cytometry. We then explored possible roles of the crosstalk between intracellular labile zinc signaling and nitric oxide signaling in TPEN-triggered apoptosis. Results: we found that TPEN induced apoptosis in NB4 APL cells in a dosage-dependent manner. We further demonstrated that TPEN triggered apoptosis by attenuating intracellular zinc and nitric oxide signaling in NB4 cells. Both exogenous zinc supplement and the nitric donor sodium nitroprusside (SNP) pre-incubation reversed TPEN-mediated inhibition of intracellular NO and Zn²⁺ signaling, and rescued NB4 cells from apoptosis. Conclusion: These results suggest for the first time that crosstalk between zinc signaling and nitric oxide pathway is essential for the survival of NB4 cells. TPEN induces apoptosis in NB4 cells via negatively regulating intracellular NO and Zn²⁺ signaling. Our in vitro data suggest that zinc depletion by TPEN may be a potential therapeutic strategy for APL.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zhu

Wang

Zhou

et al. 2017

Cell Physiol Biochem

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“…The decrease in NO system activity was observed even when these animals were fed an adequate zinc diet during postweaning life, suggesting that this fetal injury can program the functional capacity of the NO system in adulthood. In this regard, we have demonstrated that moderate zinc deficiency during fetal and postnatal growth induces similar effects in renal and cardiac NO systems [18,21,22,56].…”

Section: Discussionmentioning

confidence: 87%

“…Lipid oxidative damage in aortic slices was evaluated by measuring the formation of 2-thiobarbituric acid reactive substances (TBARS) as previously described [22,38]. Aortic slices from 6-and 81-day-old rats of both sexes were homogenized (Pro 200, Pro Scientific Inc., Oxford, CT, USA) in 30 mM potassium phosphate buffer and 120 mM KCl, pH 7.4 (1/12 w/v), and centrifuged at 2500 rpm for 10 min at 4°C.…”

Section: Aortic Oxidative Stressmentioning

confidence: 99%

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Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats

Abregú

Gobetto

Juriol

et al. 2018

The Journal of Nutritional Biochemistry

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Micronutrient malnutrition during intrauterine and postnatal growth may program cardiovascular diseases in adulthood. We examined whether moderate zinc restriction in male and female rats throughout fetal life, lactation and/or postweaning growth induces alterations that can predispose to the onset of vascular dysfunction in adulthood. Female Wistar rats were fed low- or control zinc diets from pregnancy to offspring weaning. After weaning, offspring were fed either a low- or a control zinc diet until 81 days. We evaluated systolic blood pressure (SBP), thoracic aorta morphology, nitric oxide (NO) system and vascular reactivity in 6- and/or 81-day-old offspring. At day 6, zinc-deficient male and female offspring showed a decrease in aortic NO synthase (NOS) activity accompanied by an increase in oxidative stress. Zinc-deficient 81-day-old male rats exhibited an increase in collagen deposition in tunica media, as well as lower activity of endothelial NOS (eNOS) that could not be reversed with an adequate zinc diet during postweaning life. Zinc deficiency programmed a reduction in eNOS protein expression and higher SBP only in males. Adult zinc-deficient rats of both sexes showed reduced vasodilator response dependent on eNOS activity and impaired aortic vasoconstrictor response to angiotensin-II associated with alterations in intracellular calcium mobilization. Female rats were less sensitive to the effects of zinc deficiency and exhibited higher eNOS activity and/or expression than males, without alterations in SBP or aortic histology. This work strengthens the importance of a balanced intake of micronutrients during perinatal growth to ensure adequate vascular function in adult life.

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Associations of trace elements in blood with the risk of isolated ventricular septum defects and abnormal cardiac structure in children

Zhu

Zhang

et al. 2019

Environ Sci Pollut Res

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Cardiac changes in apoptosis, inflammation, oxidative stress, and nitric oxide system induced by prenatal and postnatal zinc deficiency in male and female rats

Abstract: Prenatal and postnatal zinc deficiency induces alterations in cardiac apoptotic, inflammatory, oxidative, and nitric oxide pathways that could predispose the onset of cardiovascular diseases in adult life.

Cited by 19 publications

References 66 publications

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Developmental programming of vascular dysfunction by prenatal and postnatal zinc deficiency in male and female rats

Associations of trace elements in blood with the risk of isolated ventricular septum defects and abnormal cardiac structure in children

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