Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes

James L. Borke; Gary M. Whitford

doi:10.1093/jn/129.6.1209

Chronic fluoride ingestion decreases ⁴⁵Ca uptake by rat kidney membranes

James L. Borke, Gary M. Whitford

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

High exposures to fluoride (F^-) may occur in environments rich in F^- from natural or industrial sources and from misuse of F^- containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F^- have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F^- ingestion on ATP-dependent ⁴⁵Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F^- alters Ca⁺⁺ transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F^- (0.9 mg/L), semi-purified diet with a Ca⁺⁺ concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F^- at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F^- levels of <0.4, 2, 7, or 35 μmol/L, respectively. ATP-dependent ⁴⁵Ca uptake was significantly lower in the 150 mg F^-/L exposure group than in the 0 mg F^- /L controls (P < 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca⁺⁺-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca⁺⁺-pump (P < 0.05, 150 mg F^-/L group versus control) and endoplasmic reticulum Ca⁺⁺-pump (P < 0.05 for both the 50 and 150 mg F^-/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca⁺⁺-pump antibodies showed less (P < 0.05) endoplasmic reticulum Ca⁺⁺- pump protein and plasma membrane Ca⁺⁺-pump protein in all treatment groups than controls. Both Ca⁺⁺-pumps are transport molecules of great importance in the regulation of Ca⁺⁺ homeostasis. Our study suggests that chronic, high F^- ingestion producing high plasma F^- levels may occur in humans and may affect Ca⁺⁺ homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca⁺⁺-pump proteins.

Original language	English (US)
Pages (from-to)	1209-1213
Number of pages	5
Journal	Journal of Nutrition
Volume	129
Issue number	6
DOIs	https://doi.org/10.1093/jn/129.6.1209
State	Published - 1999
Externally published	Yes

Keywords

Ca transport
Ca-pump
Endoplasmic reticulum Ca- pump
Fluoride
Plasma membrane Ca-pump
Rats

ASJC Scopus subject areas

Medicine (miscellaneous)
Nutrition and Dietetics

Access to Document

10.1093/jn/129.6.1209

Cite this

@article{ef13e62701054edbac281fcbf3c8faaa,

title = "Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes",

abstract = "High exposures to fluoride (F-) may occur in environments rich in F- from natural or industrial sources and from misuse of F- containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F- have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F- ingestion on ATP-dependent 45Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F- alters Ca++ transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F- (0.9 mg/L), semi-purified diet with a Ca++ concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F- at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F- levels of <0.4, 2, 7, or 35 μmol/L, respectively. ATP-dependent 45Ca uptake was significantly lower in the 150 mg F-/L exposure group than in the 0 mg F- /L controls (P < 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca++-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca++-pump (P < 0.05, 150 mg F-/L group versus control) and endoplasmic reticulum Ca++-pump (P < 0.05 for both the 50 and 150 mg F-/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca++-pump antibodies showed less (P < 0.05) endoplasmic reticulum Ca++- pump protein and plasma membrane Ca++-pump protein in all treatment groups than controls. Both Ca++-pumps are transport molecules of great importance in the regulation of Ca++ homeostasis. Our study suggests that chronic, high F- ingestion producing high plasma F- levels may occur in humans and may affect Ca++ homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca++-pump proteins.",

keywords = "Ca transport, Ca-pump, Endoplasmic reticulum Ca- pump, Fluoride, Plasma membrane Ca-pump, Rats",

author = "Borke, {James L.} and Whitford, {Gary M.}",

year = "1999",

doi = "10.1093/jn/129.6.1209",

language = "English (US)",

volume = "129",

pages = "1209--1213",

journal = "Journal of Nutrition",

issn = "0022-3166",

publisher = "American Society for Nutrition",

number = "6",

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TY - JOUR

T1 - Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes

AU - Borke, James L.

AU - Whitford, Gary M.

PY - 1999

Y1 - 1999

N2 - High exposures to fluoride (F-) may occur in environments rich in F- from natural or industrial sources and from misuse of F- containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F- have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F- ingestion on ATP-dependent 45Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F- alters Ca++ transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F- (0.9 mg/L), semi-purified diet with a Ca++ concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F- at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F- levels of <0.4, 2, 7, or 35 μmol/L, respectively. ATP-dependent 45Ca uptake was significantly lower in the 150 mg F-/L exposure group than in the 0 mg F- /L controls (P < 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca++-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca++-pump (P < 0.05, 150 mg F-/L group versus control) and endoplasmic reticulum Ca++-pump (P < 0.05 for both the 50 and 150 mg F-/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca++-pump antibodies showed less (P < 0.05) endoplasmic reticulum Ca++- pump protein and plasma membrane Ca++-pump protein in all treatment groups than controls. Both Ca++-pumps are transport molecules of great importance in the regulation of Ca++ homeostasis. Our study suggests that chronic, high F- ingestion producing high plasma F- levels may occur in humans and may affect Ca++ homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca++-pump proteins.

AB - High exposures to fluoride (F-) may occur in environments rich in F- from natural or industrial sources and from misuse of F- containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F- have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F- ingestion on ATP-dependent 45Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F- alters Ca++ transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F- (0.9 mg/L), semi-purified diet with a Ca++ concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F- at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F- levels of <0.4, 2, 7, or 35 μmol/L, respectively. ATP-dependent 45Ca uptake was significantly lower in the 150 mg F-/L exposure group than in the 0 mg F- /L controls (P < 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca++-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca++-pump (P < 0.05, 150 mg F-/L group versus control) and endoplasmic reticulum Ca++-pump (P < 0.05 for both the 50 and 150 mg F-/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca++-pump antibodies showed less (P < 0.05) endoplasmic reticulum Ca++- pump protein and plasma membrane Ca++-pump protein in all treatment groups than controls. Both Ca++-pumps are transport molecules of great importance in the regulation of Ca++ homeostasis. Our study suggests that chronic, high F- ingestion producing high plasma F- levels may occur in humans and may affect Ca++ homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca++-pump proteins.

KW - Ca transport

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KW - Endoplasmic reticulum Ca- pump

KW - Fluoride

KW - Plasma membrane Ca-pump

KW - Rats

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