The Role of Cell Calcium in Current Approaches to Toxicology

Pounds, Joel G.

doi:10.2307/3430699

Cited by 7 publications

(5 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Figure 1). The concentration of Ca2 + in extracellular fluids is M and in the cytosol approximately l o p 7 M. The processes that maintain this large concentration gradient are extraordinary intricate, and there is evidence that events at the plasma, endoplasmic reticulum, and mitochondria1 membranes are all involved interactively in regulating the intracellular ion concentration (5). Data indicate that acetaminophen and its principal toxic metabolite N-acetyl-p-benzoquinone imine induce hepatic necrosis by a cellular oxidative stress resulting in lipid peroxidation and a change in the intracellular Ca2 + homeostasis (6).…”

Section: Methodsmentioning

confidence: 99%

Calcium channel blocking agents protect against acetaminophen‐induced cytotoxicity in rat hepatocytes

Thibault¹,

Peytavin²,

Claude³

1991

J. Biochem. Toxicol.

View full text Add to dashboard Cite

The effect on acetaminophen-induced cytotoxicity of three calcium channel blocking agents--diltiazem, verapamil and gallopamil--was studied in primary cultures of rat hepatocytes and compared with the chelating agent EGTA. Using the measurement of cytosolic lactate dehydrogenase (LDH) as an index of cytotoxicity, it was demonstrated that a 1-hr pretreatment with calcium channel blocking agents protected cells against acetaminophen cytotoxicity, but were less effective than EGTA. These data suggest that influx of extracellular Ca2+ into the cells could have a role in the genesis of hepatocyte injury by acetaminophen.

show abstract

Section: Methodsmentioning

confidence: 99%

Calcium channel blocking agents protect against acetaminophen‐induced cytotoxicity in rat hepatocytes

Thibault¹,

Peytavin²,

Claude³

1991

J. Biochem. Toxicol.

View full text Add to dashboard Cite

show abstract

“…The impaired generation of a cAMP signal could be exacerbated by Pb2+-calmodulin dependent activation of phosphodiesterase, thereby degrading cyclic nucleotides (136). In actuality, the spatial and temporal aspects of cAMP and Ca2+ signals are so complex as to preclude prediction of toxicity based on simple observations in cell-free systems (113,114). In fact, studies of parallel cAMPand Ca2+-mediated hormonal inhibition of pyruvate kinase found no effects of lead on Ca2+-mediated processes, but not cAMP processes (144).…”

Section: Modulating Systemsmentioning

confidence: 99%

Cellular and molecular toxicity of lead in bone.

Pounds

Long

Rosen

1991

Environ Health Perspect

292

131

View full text Add to dashboard Cite

To fully understand the significance of bone as a target tissue of lead toxicity, as well as a reservoir of systemic lead, it is necessary to define the effects of lead on the cellular components of bone. Skeletal development and the regulation of skeletal mass are ultimately determined by the four different types of cells: osteoblasts, lining cells, osteoclasts, and osteocytes. These cells, which line and penetrate the mineralized matrix, are responsible for matrix formation, mineralization, and bone resorption, under the control of both systemic and local factors. Systemic components of regulation include parathyroid hormone, 1,25-dihydroxyvitamin D3, and calcitonin: local regulators include numerous cytokines and growth factors. Lead intoxication directly and indirectly alters many aspects of bone cell function. First, lead may indirectly alter bone cell function through changes in the circulating levels of those hormones, particularly 1,25-dihydroxyvitamin D3, which modulate bone cell function. These hormonal changes have been well established in clinical studies, although the functional significance remains to be established. Second, lead may directly alter bone cell function by perturbing the ability of bone cells to respond to hormonal regulation. For example, the 1,25-dihydroxyvitamin D3-stimulated synthesis of osteocalcin, a calcium-binding protein synthesized by osteoblastic bone cells, is inhibited by low levels of lead. Impaired osteocalcin production may inhibit new bone formation, as well as the functional coupling of osteoblasts and osteoclasts. Third, lead may impair the ability of cells to synthesize or secrete other components of the bone matrix, such as collagen or bone sialoproteins (osteopontin). Finally, lead may directly effect or substitute for calcium in the active sites of the calcium messenger system, resulting in loss of physiological regulation. The effects of lead on the recruitment and differentiation of bone cells remains to be established. Compartmental analysis indicates that the kinetic distribution and behavior of intracellular lead in osteoblasts and osteoclasts is similar to several other cell types. Many of the toxic effects of lead on bone cell function may be produced by perturbation of the calcium and cAMP messenger systems in these cells.

show abstract

“…This is ensured by various Ca# + transport systems, such as channels, ATP-driven pumps, exchanger proteins and Ca# + -binding proteins [4,5]. Perturbations of Ca# + -mediated signal transduction have been considered as underlying mechanisms for the action of various chemical toxicants [6,7]. Transient increases in intracellular free Ca# + and subsequent activation of protein kinases modulate cell proliferation and\or differentiation [8], whereas persistent elevation of the Ca# + concentration might be associated with necrotic or, in certain systems, apoptotic processes [9,10].…”

Section: Introductionmentioning

confidence: 99%

Study of the interactions of cadmium and zinc ions with cellular calcium homoeostasis using 19F-NMR spectroscopy

Benters

Flögel

Schäfer

et al. 1997

Biochemical Journal

100

View full text Add to dashboard Cite

The effects of the heavy-metal ions Cd2+ and Zn2+ on the homoeostasis of intracellular free Ca2+ in E367 neuroblastoma cells were examined using 19F-NMR spectroscopy with the fluorinated chelator probe 1,2-bis-(2-amino-5-fluorophenoxy)ethane-N,N,N', N'-tetra-acetic acid (5F-BAPTA). First, the technique was used to quantify the uptake and intracellular free concentrations of the heavy metals after treatment of the cells with 20 microM CdCl2 or 100 microM ZnCl2. Secondly, metal-induced transients in intracellular free Ca2+ were recorded. Addition of 20 microM CdCl2, but not 100 microM ZnCl2, evoked a transient increase in Ca2+ from a resting level of 84 nM to approx. 190 nM within 15 min after addition of the metal. Zn2+ at 20 microM completely prevented the induction of a Ca2+ transient by Cd2+. Ca2+ was mobilized by Cd2+ from intracellular organelles, since depletion of these stores by thapsigargin abolished the effect of the toxic metal. Furthermore, 20 microM Cd2+ evoked a transient rise in cellular Ins(1,4,5)P3, reaching a maximum level within 5 min after addition of the metal. These results demonstrate that perturbation of the Ins(1,4,5)P3/Ca2+ messenger system is an early and discrete cellular effect of Cd2+.

show abstract

The Role of Cell Calcium in Current Approaches to Toxicology

Cited by 7 publications

References 38 publications

Calcium channel blocking agents protect against acetaminophen‐induced cytotoxicity in rat hepatocytes

Calcium channel blocking agents protect against acetaminophen‐induced cytotoxicity in rat hepatocytes

Cellular and molecular toxicity of lead in bone.

Study of the interactions of cadmium and zinc ions with cellular calcium homoeostasis using 19F-NMR spectroscopy

Contact Info

Product

Resources

About