Excessive intracellular zinc accumulation in cardiac and skeletal muscles of dystrophic hamsters

Crawford, Alice J.; Bhattacharya, Syamal K.

doi:10.1016/0014-4886(87)90137-3

Cited by 35 publications

(25 citation statements)

References 30 publications

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“…These findings underscore the clinical relevance of both pharma- and nutriceutical strategies that can uncouple the coupled dyshomeostasis of these biologically essential cations and modulate them in favor of sustained antioxidant defenses. The coupled Ca 2+ and Zn 2+ dyshomeostasis seen in aldosteronism resembles the Ca 2+ overloading and oxidative stress that exists in the hearts of hamsters with hereditary muscular dystrophy which is also accompanied by increased tissue Zn 2+ [75–79]. This divalent cation dyshomeostasis seen in muscular dystrophy could be prevented by parathyroidectomy or a Ca 2+ channel blocker.…”

Section: Cellular and Molecular Pathways Leading To Cardiomyocyte Necmentioning

confidence: 99%

Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

et al. 2010

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Fibrosis is a fundamental component of the adverse structural remodeling of myocardium present in the failing heart. Replacement fibrosis appears at sites of previous cardiomyocyte necrosis to preserve the structural integrity of the myocardium, but not without adverse functional consequences. The extensive nature of this microscopic scarring suggests cardiomyocyte necrosis is widespread and the loss of these contractile elements, combined with fibrous tissue deposition in the form of a stiff in-series and in-parallel elastic elements, contributes to the progressive failure of this normally efficient muscular pump. Cellular and molecular studies into the signaltransducer-effector pathway involved in cardiomyocyte necrosis have identified the crucial pathogenic role of intracellular Ca 2+ overloading and subsequent induction of oxidative stress, Correspondence to: Karl T. Weber, KTWeber@uthsc.edu. NIH Public Access Author ManuscriptHeart Fail Rev. Author manuscript; available in PMC 2012 January 1. Published in final edited form as:Heart Fail Rev. 2011 January ; 16(1): 23-34. doi:10.1007/s10741-010-9169-3. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript predominantly confined within its mitochondria, to be followed by the opening of the mitochondrial permeability transition pore that leads to the destruction of these organelles and cells. It is now further recognized that Ca 2+ overloading of cardiac myocytes and mitochondria serves as a prooxidant and which is counterbalanced by an intrinsically coupled Zn 2+ entry serving as antioxidant. The prospect of raising antioxidant defenses by increasing intracellular Zn 2+ with adjuvant nutriceuticals can, therefore, be preferentially exploited to uncouple this intrinsically coupled Ca 2+ -Zn 2+ dyshomeostasis. Hence, novel yet simple cardioprotective strategies may be at hand that deserve to be further explored.

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Section: Cellular and Molecular Pathways Leading To Cardiomyocyte Necmentioning

confidence: 99%

Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

et al. 2010

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“…The coupled Ca 2+ and Zn 2+ dyshomeostasis seen in aldosteronism resembles the Ca 2+ overloading and oxidative stress mirrored in the hearts of hamsters with hereditary muscular dystrophy, which is also accompanied by increased tissue Zn 2+ . [93][94][95][96][97] This divalent cation dyshomeostasis seen in muscular dystrophy could be prevented by parathyroidectomy or a Ca 2+ channel blocker. 95 production, cardiomyocyte xanthine oxidase activity, and cardiac and mitochondrial 8-isoprostane levels, counterbalanced by increased activity of antioxidant proteins, enzymes and the non-enzymatic antioxidants that can be considered together as cumulative antioxidant capacity.…”

Section: Zinc Dyshomeostasis In Aldosteronismmentioning

confidence: 99%

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

et al. 2010

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Inappropriately (relative to dietary Na + ) elevated plasma aldosterone concentrations (PAC), or aldosteronism, have been incriminated in both the appearance of the cardiometabolic syndrome (CMS) and its progressive nature. The deleterious dual consequences of elevated PAC and dietary Na + have been linked to several components of the CMS, including salt-sensitive hypertension. Moreover, their adverse consequences are considered to be synergistic, culminating in a pro-oxidant phenotype with oxidative injury involving the heart and systemic tissues, including peripheral blood mononuclear cells (PBMC). Our experimental studies in rats receiving aldosterone/salt treatment have identified a common pathogenic event that links aldosteronism to the induction of oxidative stress. Herein, we review these findings and the important role of excessive intracellular Ca 2+ accumulation (EICA), or intracellular Ca 2+ overloading, which occurs in the heart and PBMC, leading to, respectively, cardiomyocyte necrosis with a replacement fibrosis and an immunostimulatory state with consequent coronary vasculopathy. The origin of EICA is based on elevations in plasma parathyroid hormone, which are integral to the genesis of secondary hyperparathyroidism that accompanies aldosteronism and occurs in response to plasma-ionized hypocalcemia and hypomagnesemia whose appearance is the consequence of marked urinary and fecal excretory losses of Ca 2+ and Mg 2+ . In addition, we found intracellular Ca 2+ overloading to be intrinsically coupled to a dyshomeostasis of intracellular Zn 2+ , which together regulate the redox state of cardiac myocytes and mitochondria via the induction of oxidative stress and generation of antioxidant defenses, respectively. To validate our hypothesis, a series of site-directed, sequential pharmacological and/or nutriceutical interventions targeted along cellular-molecular cascades were carried out to either block downstream events leading to the pro-oxidant phenotype or to enhance antioxidant defenses. In each case, the interventions were found to be cardioprotective. These cumulative salutary responses raise the prospect that pharmacological agents and nutriceuticals capable of influencing extra-and intracellular Ca 2+ and Zn 2+ equilibrium could prevent adverse cardiac remodeling and thereby enhance the management of aldosteronism.

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“…group (P c 0.01). More extensive total Zn and Cu analyses [28] on the breast and leg muscles of fifteen white leghorn chickens have also been carried out. In the breast muscle, the Zn and Cu concentrations were 0.26 + 0.03 and 0.024 f 0.002 mmol/kg of dry weight, respectively.…”

Section: Metal Contents Of Breast and Leg ~~S~~es Obadiah Speciesmentioning

confidence: 99%

An unusual metal‐binding cluster found exclusively in the avian breast muscle troponin T of Galliformes and Craciformes

Jin¹,

Smillie²

1994

FEBS Letters

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A repeating metal-binding (Cu'+ > Ni*+ > Zn" -Co") sequence (HE/AEAH), has been identified in troponin T isoforms specifically expressed in the breast but not leg muscles of all Galliformes and Craciformes. It is absent in the skeletal and cardiac muscles of mammals and all other avian species investigated. Concentration of the metal-binding sites is adequate to affect free metal levels in the muscle cell and we suggest a possible link between its presence in breast muscle of Gallijormes and the high ratio of breast muscle to total body muscle mass and explosive but short-lived flight pattern of these birds. This sequence can be used for a highly selective metal-affinity chromatographic purification of muscle or engineered TnTs even in high salt and/or urea.

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Excessive intracellular zinc accumulation in cardiac and skeletal muscles of dystrophic hamsters

Cited by 35 publications

References 30 publications

Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

Cellular and molecular pathways to myocardial necrosis and replacement fibrosis

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

An unusual metal‐binding cluster found exclusively in the avian breast muscle troponin T of Galliformes and Craciformes

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