Risk of High Dietary Calcium for Arterial Calcification in Older Adults -Review

Risk of High Dietary Calcium for Arterial Calcification in Older Adults -Review
Nutrients 2013, 5, 3964-3974; doi:10.3390 / nu5103964 / ISSN 2072-6643

Abstract:

 

Concern has recently arisen about the potential adverse effects of excessive calcium intakes, i.e., calcium loading from supplements, on arterial calcification and risks of cardiovascular diseases (CVD) in older adults. Published reports that high calcium intakes in free-living adults have relatively little or no beneficial impact on bone mineral density (BMD) and fracture rates suggest that current recommendations of calcium for adults may be set too high. Because even healthy kidneys have limited capability of eliminating excessive calcium in the diet, the likelihood of soft-tissue calcification may increase in older adults who take calcium supplements, particularly in those with age or disease-related reduction in renal function. The maintenance of BMD and bone health continues to be an important goal of adequate dietary calcium consumption, but eliminating potential risks of CVDs from excessive calcium intakes needs to be factored into policy recommendations for calcium by adults.

Chronic Iron Deficiency as an Emerging Risk Factor for Osteoporosis: A Hypothesis (Review)

Chronic Iron Deficiency as an Emerging Risk Factor for Osteoporosis: A Hypothesis (Review)

Chronic Iron Deficiency as an Emerging Risk Factor for Osteoporosis: A Hypothesis (Review)

Laura Toxqui and M. Pilar Vaquero *

Abstract:

Iron is essential in oxygen transport and participates in many enzymatic systems in the body, with important roles in collagen synthesis and vitamin D metabolism. The relationship between iron and bone health comes from clinical observations in iron overload patients who suffered bone loss. The opposite scenario—whether iron deficiency, with or without anemia, affects bone metabolism—has not been fully addressed. This is of great interest, as this nutrient deficiency is a worldwide public health problem and at the same time osteoporosis and bone alterations are highly prevalent. This review presents current knowledge on nutritional iron deficiency and bone remodeling, the biomarkers to evaluate iron status and bone formation and resorption, and the link between iron and bone metabolism. Finally, it is hypothesized that chronic iron deficiency induces bone resorption and risk of osteoporosis, thus complete recovery from anemia and its prevention should be promoted in order to improve quality of life including bone health. Several mechanisms are suggested; hence, further investigation on the possible impact of chronic iron deficiency on the development of osteoporosis is needed.



 

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1

 

 PalmieriV PapaleoV PorcelliP ScarciaL GaitaR SaccoJ HagerF RousseauP CuratoloB ManziR MiliterniC BravaccioS TrilloC SchneiderR MelmedM EliaC LentiM SaccaniT PascucciS Puglisi-AllegraK-L Reichelt & A M Persico

 

Abstract

 

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient–control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca2+). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca2+ chelator ethylene glycol tetraacetic acid; neocortical Ca2+ levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca2+-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca2+ levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca2+ homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.

Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways

Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways
ElsevierBiochimica et Biophysica Acta (BBA) – Molecular Cell Research
Volume 1865, Issue 11, Part B, November 2018, Pages 1718-1732

Intracellular calcium dysregulation in autism spectrum disorder: An analysis of converging organelle signaling pathways

Interleukin-1beta Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin*

Interleukin-1beta Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin*

Interleukin-1 Processing Is Dependent on a Calcium-mediated Interaction with Calmodulin*

 

Joseph S. Ainscough‡1, G. Frank Gerberick§, Ian Kimber‡, and Rebecca J. Dearman‡
From the ‡ Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom and the § Procter & Gamble Co. , Cincinnati, Ohio 45253

 

The secretion of IL-1 is a central event in the initiation of inflammation. Unlike most other cytokines, the secretion of IL-1 requires two signals: one signal to induce the intracellular up-regulation of pro-IL-1 and a second signal to drive secretion of the bioactive molecule. The release of pro-IL-1is a complex process involving proteolytic cleavage by caspase-1. However, the exact mechanism of secretion is poorly understood. Here we sought to identify novel proteins involved in IL-1 secretion and intracellular processing to gain further insights into the mechanism of IL-1 release. A human proteome microarray containing 19,951 unique proteins was used to identify proteins that bind human recombinant pro-IL-1. Probes with a signal-to-noise ratio of >3 were defined as biologically relevant. In these analyses, calmodulin was identified as a particularly strong hit, with a signal-to-noise ratio of 11. Using an ELISA-based protein-binding assay, the interaction of recombinant calmodulin with pro-IL-1, but not mature IL-1, was confirmed and shown to be calcium-dependent. Finally, using small molecule inhibitors, it was demonstrated that both calcium and calmodulin were required for nigericin-induced IL-1 secretion in THP-1 cells and primary human monocytes. Together, these data suggest that, following calcium influx into the cell, pro-IL-1 interacts with calmodulin and that this interaction is important for IL-1 processing and release.

Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study

Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study

Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study

Jacquelaine Bartlett, MS,#1 Irene M. Predazzi, PhD,#2 Scott M. Williams, PhD,1 William S. Bush, PhD, MS,3Yeunjung Kim, MD, MPH,4 Stephen Havas, MD, MPH, MS,5 Peter P. Toth, MD, PhD,6 Sergio Fazio, MD, PhD,2 andMichael Miller, MD7

 

 

Abstract

Background—

While the inverse association between high-density lipoprotein cholesterol (HDLC) and risk of (CVD) has been long established, it remains unclear whether low HDL-C remains a CVD risk factor when levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) are not elevated. This is a timely issue because recent studies have questioned whether HDLC is truly an independent predictor of CVD.

Methods and Results—

3590 men and women from the Framingham Heart Study offspring cohort without known CVD were followed between 1987 and 2011. Low HDL-C (<40 mg/dL in men and <50 mg/dL in women) was defined as “isolated” if TG and LDL-C were both low (<100 mg/dL). We also examined higher thresholds for TG (150 mg/dL) and LDL-C (130 mg/dL) and compared low versus high HDL-C phenotypes using logistic regression analysis to assess association with CVD. Compared to isolated low HDL-C, CVD risks were higher when low HDLC was accompanied by LDL-C ≥100 mg/dL and TG <100 mg/dL (OR 1.3 [1.0, 1.6]), TG ≥100mg/dL and LDL-C <100 mg/dL (OR 1.3 [1.1, 1.5]), or TG and LDL-C ≥ 100 mg/dL (OR 1.6, [1.2,2.2]), after adjustment for covariates. When low HDL-C was analyzed with higher thresholds for TG (≥150 mg/dL) and/or LDL-C (≥130 mg/dL) results were essentially the same. In contrast,compared to isolated low HDL-C, high HDL-C was associated with 20-40% lower CVD risk except when TG and LDL-C were elevated.

Conclusions—

CVD risk as a function of HDL-C phenotypes is modulated by other components
of the lipid panel.

Read full articles here.

HDL cholesterol and bone mineral density: Is there a genetic link?

HDL cholesterol and bone mineral density: Is there a genetic link?

HDL cholesterol and bone mineral density: Is there a genetic link?

Cheryl L. Ackert-Bicknell

 

Abstract

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high-density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.

Read full article here

Calcium aids chromosome condensation prior to cell division

Calcium aids chromosome condensation prior to cell division
Science News
from research organizations

Calcium aids chromosome condensation prior to cell division

Date:
December 27, 2016
Source:
Osaka University
Summary:
New research reveals role for calcium ions in chromosome condensation during mitosis; high-resolution imaging of living cells reveals compact, globular chromosomes in the presence of calcium that became fibrous and expand in its absence.
FULL STORY

Osaka University-led Japanese research reveals role for calcium ions in chromosome condensation during mitosis; high-resolution imaging of living cells reveals compact, globular chromosomes in the presence of calcium that became fibrous and expand in its absence.

Before cell division when a parent cell divides into two daughter cells, each with an identical set of genetic information, replicated chromosomes become condensed and align along the spindle in the middle of the cell. This is the metaphase stage of mitosis. Chromosomes are made up of strands of DNA wrapped around histones, forming nucleosomes that resemble beads on a string. The chromosome structure is maintained by histone changes, chromosome scaffold proteins, and positively charged ions (cations). However, removal of scaffold proteins has no effect on chromosome condensation, suggesting that another factor causes the organization of metaphase chromosomes. Now, work led by Osaka University has revealed that calcium ions (Ca2+) play a crucial role in chromatin fiber compaction. The study was reported in Scientific Reports.

Calcium is a universal second messenger with many functions, including progression of the cell cycle. During mitosis, both Ca2+and magnesium ions (Mg2+) are released from storage organelles to bind chromatin, though 6-8-fold more Ca2+ is bound than Mg2+suggesting that it has a more important role. A research team led by Hideaki Takata, Kiichi Fukui and Rinyaporn Phengchat at Osaka University first confirmed that Ca2+ is necessary to prevent chromosome misalignment during mitosis, then used an imaging assessment of molecular interactions based on fluorescence decay (FLIM-FRET) to show that chromosomes were less compact in the absence of intracellular Ca2+.

This same imaging process also revealed that changes in Ca2+levels of living HeLa cells altered the extent of chromosome compaction, with the re-addition of Ca2+ causing chromosome compaction. Ca2+ therefore appears to control the transition between condensation and decondensation. “Although previous studies have demonstrated nucleosome packaging using isolated chromatin” study first author Rinyaporn Phengchat says, “such findings should be confirmed in vivo as we have done using the sensitive FLIM-FRET technique which provides a high level of spatial resolution.”

The team then used scanning electron microscopy to visualize chromosome structures at very high resolution. “Ca2+ has a concentration-dependent effect on chromosome structure,” corresponding author Hideaki Takata explains, “causing chromosomes to change from expanded fibrous structures to compact globular structures with increasing levels of Ca2+.”

The researchers propose that, in the absence of Ca2+, the negatively charged DNA is less well neutralized, preventing it from condensing and delaying entry into prometaphase of the cell cycle. “We think that a lack of Ca2+ disturbs the organization of chromosomes at the spindle, causing them to misalign,” corresponding author Kiichi Fukui says. “Conversely, the normal rising levels of Ca2+ during mitosis promote chromosome condensation after breakdown of the nuclear envelope.”

Story Source:

Materials provided by Osaka UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Rinyaporn Phengchat, Hideaki Takata, Kenichi Morii, Noriko Inada, Hideji Murakoshi, Susumu Uchiyama, Kiichi Fukui. Calcium ions function as a booster of chromosome condensationScientific Reports, 2016; 6: 38281 DOI: 10.1038/srep38281

 

Cancer-Related Hypercalcemia

Cancer-Related Hypercalcemia

University of Nebraska Medical Center, Omaha, NE

Abstract

Hypercalcemia has been reported to occur in up to30%of patients whohave a malignancy. Hypercalcemia is most common in those who have later-stage malignancies and predicts a poor prognosis for those with it. The most common causes include humoral hypercalcemia of malignancy mediated by parathyroid hormone–related peptide, osteolytic cytokine production, and excess 1,25-dihydroxy  VitaminD production. However, the etiology is not always mediated by malignancy. Hypercalcemia can occur in those with malignancy and an additional etiology for hypercalcemia such as primary hyperparathyroidism or granulomatous diseases. This paper reviews the cancers associated with hypercalcemia and their proposed mechanisms, nontumor-mediated hypercalcemia, as well as diagnosis
and treatment strategies for each condition.

Read full Article here…

Modeling and Analysis of Calcium Signaling Events Leading to Long-Term Depression in Cerebellar Purkinje Cells

Modeling and Analysis of Calcium Signaling Events Leading to Long-Term Depression in Cerebellar Purkinje Cells

Nicholas Hernjak, Boris M. Slepchenko, Kathleen Fernald, Charles C. Fink, Dale Fortin, Ion I. Moraru, James Watras, and Leslie M. Loew Center for Cell Analysis and Modeling, University of Connecticut Health Center, armington, Connecticut

Abstract

Modeling and simulation of the calcium signaling events that precede long-term depression of synaptic activity in cerebellar Purkinje cells are performed using the Virtual Cell biological modeling framework. It is found that the unusually high density and low sensitivity of inositol-1,4,5-trisphosphate receptors (IP3R) are critical to the ability of the cell to generate and localize a calcium spike in a single dendritic spine. The results also demonstrate the model’s capability to simulate the supralinear calcium spike observed experimentally during coincident activation of the parallel and climbing fibers. The sensitivity of the calcium spikes to certain biological and geometrical effects is investigated as well as the mechanisms that underlie the cell’s ability to generate the supralinear spike. The sensitivity of calcium release rates from the IP3R to calcium concentrations, as well as IP3 concentrations, allows the calcium spike to form. The diffusion barrier caused by the small radius of the spine neck is shown to be important, as a threshold radius is observed above which a spike cannot be formed. Additionally, the calcium buffer capacity and diffusion rates from the spine are found to be important parameters in shaping the calcium spike.