Cardiac Hypertrophy in Rats with Iron and Copper Deficiency: Quantitative Contribution of Mitochondrial Enlargement

Goodman, Joshua; Warshaw, Joseph B.; Dallman, Peter R.

doi:10.1203/00006450-197005000-00003

Cited by 106 publications

(35 citation statements)

References 15 publications

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“…The increase in heart weight is due to muscle, 2 and the associated increase in mitochondrial mass 5 may be sufficient to account for 75% of the total increase in heart weight. 6 Hypertrophy regressed with iron therapy and the increased ratio of mitochondrial to myofibrillar area seen on electron microscopic section returned to normal. 8 Despite dramatic changes in mitochondrial morphology the P/O ratios remained normal, 6 indicating that there was no loss of sites of oxidative phosphorylation, although iron deficiency does impair oxidative phosphorylation at site 1 in the yeast Torulopsis utilis.…”

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confidence: 94%

“…6 Hypertrophy regressed with iron therapy and the increased ratio of mitochondrial to myofibrillar area seen on electron microscopic section returned to normal. 8 Despite dramatic changes in mitochondrial morphology the P/O ratios remained normal, 6 indicating that there was no loss of sites of oxidative phosphorylation, although iron deficiency does impair oxidative phosphorylation at site 1 in the yeast Torulopsis utilis. ' 1 Site I depends on the presence of non-heme iron.…”

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confidence: 94%

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The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.

Blayney¹,

Bailey-Wood²,

Jacobs³

et al. 1976

Circulation Research

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SUMMARYWe have examined the effects of total body iron deficiency on the function of mitochondria isolated from rat hearts. Male Wistar rats were weaned at 21 days and divided into an experimental iron-deficient group and a control group. Both groups received identical diet but an iron supplement (180 mg of ferrous sulfate per kg of diet) was added for the control group. Rats were studied at 7 and 14 weeks. Iron-deficient rats weighed less than controls but showed significantly increased ventricle to body weight ratio at both 7,and 14 weeks, indicating relative cardiac hypertrophy. Isolated mitochondrial fractions from iron-dencient and control rats contained similar proportions of whole homogenate protein and succinic cytochrome c reductase activity, indicating that the fractions isolated from the experimental and control rats were comparable. In iron-deficient rats NADH cytochrome c reductase, succinic cytochrome c reductase, succinic dehydrogenase, and NADH ferricyanide oxidoreductase activities were all significantly reduced at 7 and 14 weeks. Cytochrome c oxidase activity was significantly reduced only at 14 weeks as were the concentrations of cytochromes a 3 , c,, and b. The rate of oxygen uptake by mitochondria was significantly lower at both 7 and 14 weeks but the P/O ratio was unaltered. We conclude that iron deficiency is associated with impairment of myocardial mitochondrial electron transport.

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confidence: 94%

mentioning

confidence: 94%

The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.

Blayney¹,

Bailey-Wood²,

Jacobs³

et al. 1976

Circulation Research

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“…This decrease in plasma Cu levels could possibly have had some adverse effects on the ultrastructure of the heart in the caffeineexposed newborns. It has been shown that the heart is severely affected by Cu deficiency, Wink/Rossowska/Joseph/Yazdani/ Nakamoto leading to mitochondrial swelling [14]. Although the disturbance of cardiac mitochondria in embryonic chicks was shown previously [4], the amount of caffein used was LD40 [8].…”

Section: Discussionmentioning

confidence: 99%

Effects of Caffeine on Heart Mitochondria in Newborn Rats

Wink

Rossowska²,

Joseph³

et al. 1999

Neonatology

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Caffeine consumption has been implicated in the development of cardiovascular disease. Therefore, in the present study, litters of rats were combined upon birth, and 8 pups were randomly assigned to each dam. Dams with pups were divided into 2 groups: group 1 received a 20% protein diet as a control, and group 2 received the 20% protein diet supplemented with caffeine (4 mg/100 g body weight). Pups from both groups were killed on days 11 and 15. Transmission electron microscopy revealed swollen, disrupted, degenerating mitochondria and intracellular edema in the hearts of rats in the caffeine groups when compared with those of the controls. Plasma Cu concentration was significantly decreased. These results indicate that early exposure to caffeine through maternal milk adversely affects cardiac mitochondria of rat pups and may be associated with decreased plasma Cu levels. It is unclear whether these results apply to the human infant. Interspecies extrapolation from rat to human must be made with caution.

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“…Characteristics of the copper deficient heart include the development of concentric cardiac hypertrophy (1,2), weaknesses within the cardiac wall structure that can lead to ventricular aneurysms (2)(3)(4), and increased mitochondria proliferation (2,(5)(6)(7). Often the mitochondria have disrupted membrane microstructure and accumulation of lipid droplets (2).…”

Section: Introductionmentioning

confidence: 99%

Differential expression of genes involved with apoptosis, cell cycle, connective tissue proteins, fuel substrate utilization, inflammation and mitochondrial biogenesis in copper-deficient rat hearts: implication of a role for Nfκb1

Klaahsen

Ricklefs

Medeiros

2007

The Journal of Nutritional Biochemistry

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We hypothesized that the increase in mitochondrial proliferation in hearts from copper-deficient rats is due to an increase in expression of the transcriptional factor Ppargc1a, which regulates transcriptional activity for many of the genes that encode for mitochondrial proteins. In addition to several transcriptional factors implicated in mitochondrial biogenesis, we also looked at a number of genes involved in cell cycle regulation and fuel substrate utilization. Long-Evans rats were placed on either a copperadequate (n=4) or copper-deficient (n=4) diet 3 days post-weaning and remained on the diet for five weeks; their copper deficiency status was confirmed using previously established assays. Custom oligo arrays spotted with genes pertinent to mitochondrial biogenesis were hybridized with cRNA probes synthesized from the collected heart tissue. Chemiluminescent array images from both groups were analyzed for gene spot intensities and differential gene expression. Our results did not demonstrate any significant increase in Ppargc1a or its implicated targets, as we had predicted. However, consistent with previous data, an up-regulation of genes that encode for collagen type 3, fibronectin and elastin were found. Interestingly, there was also a significant increase in the expression of the transcriptional factor Nfκb1 in the copper-deficient treatment animals compared to the control group. The results of this study merit the further investigation of the role of ROS with regard to Nfkb1 in the copper deficient rat heart.

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Cardiac Hypertrophy in Rats with Iron and Copper Deficiency: Quantitative Contribution of Mitochondrial Enlargement

Cited by 106 publications

References 15 publications

The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.

The effects of iron deficiency on the respiratory function and cytochrome content of rat heart mitochondria.

Effects of Caffeine on Heart Mitochondria in Newborn Rats

Differential expression of genes involved with apoptosis, cell cycle, connective tissue proteins, fuel substrate utilization, inflammation and mitochondrial biogenesis in copper-deficient rat hearts: implication of a role for Nfκb1

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