Time course of electron microscopic alterations in the hypertrophied myocardium of Goldblatt rats

Wendt-Gallitelli, M. F.; Jacob, R.

doi:10.1007/bf01906363

Cited by 20 publications

(7 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also worth noting that the values for total Ca content over the enzymes' activatory range, as opposed to the higher values required for buffering, are much closer to estimates made in situ by using X-ray probe microanalysis (e.g. Somlyo et al, 1985;Wendt-Gallitelli, 1986;LeFurgey et al, 1986). These data are thus in some ways contrary to the conclusion of Nicchitta & Williamson (1984) that the effects of spermine on Ca2+ egress would allow mitochondria to buffer extramitochondrial Ca2' at lower Ca content; however, it is unclear how a process which depends on egress saturation would be affected by a change in Km.…”

Section: Discussionsupporting

confidence: 51%

Effects of spermine on mitochondrial Ca2+ transport and the ranges of extramitochondrial Ca2+ to which the matrix Ca2+-sensitive dehydrogenases respond

McCormack

1989

Biochemical Journal

View full text Add to dashboard Cite

1. Spermine has previously been reported to be an activator of mitochondrial Ca2+ uptake [Nicchitta & Williamson (1984) J. Biol. Chem. 259, 12978-12983]. This is confirmed in the present studies on rat heart, liver and kidney mitochondria by using the activities of the Ca2+-sensitive intramitochondrial dehydrogenases (pyruvate, NAD+-isocitrate and 2-oxoglutarate dehydrogenases) as probes for matrix Ca2+, and also, for the heart mitochondria, by using entrapped fura-2. 2. As also found previously [Damuni, Humphreys & Reed (1984) Biochem. Biophys. Res. Commun. 124, 95-99], spermine activated extracted pyruvate dehydrogenase phosphate phosphatase. However, it was found to have no effects at all on the extracted NAD+-isocitrate or 2-oxoglutarate dehydrogenases. It also had no effects on activities of the enzymes in mitochondria incubated in the absence of Ca2+, or on the Ca2+-sensitivity of the enzymes in uncoupled mitochondria. 3. Spermine clearly activated 45Ca uptake by coupled mitochondria, but had no effect on Ca2+ egress from mitochondria previously loaded with 45Ca. 4. Spermine (with effective Km values of around 0.2-0.4 mM) caused an approx. 2-3-fold decrease in the effective ranges of extramitochondrial Ca2+ in the activation of the Ca2+-sensitive matrix enzymes in coupled mitochondria from all of the tissues. The effects of spermine appeared to be largely independent of the other effectors of mitochondrial Ca2+ transport, such as Mg2+ (inhibitor of uptake) and Na+ (promoter of egrees). 5. In the most physiological circumstance, coupled mitochondria incubated with Na+ and Mg2+, the presence of saturating spermine (2 mM) resulted in an effective extramitochondrial Ca2+ range for matrix enzyme activation of from about 30-50 nM up to about 800-1200 nM, with half-maximal effects around 250-400 nM-Ca2+. The implications of these findings for the regulation of matrix and extramitochondrial Ca2+ are discussed.

show abstract

Section: Discussionsupporting

confidence: 51%

Effects of spermine on mitochondrial Ca2+ transport and the ranges of extramitochondrial Ca2+ to which the matrix Ca2+-sensitive dehydrogenases respond

McCormack

1989

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Anversa et al 31 demonstrated in rabbit myocardium with experimental advanced hypertrophy that the TT system was dilated. This phenomenon was then observed in other animal models of hypertrophy 32,33 and heart failure. 34 Later on, dilated TTs were also found in human heart tissues of hypertrophic cardiomyopathy, congestive cardiomyopathy, dilated cardiomyopathy, ischaemic cardiomyopathy, aortic valvular disease, and congenital heart diseases associated with obstruction to right-ventricular outflow.…”

Section: Morphological Changes Of Tts In Hypertrophy and Heart Failurementioning

confidence: 86%

Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure

Zhang

et al. 2013

Cardiovascular Research

View full text Add to dashboard Cite

AimsChronic heart failure is a complex clinical syndrome with impaired myocardial contractility. In failing cardiomyocytes, decreased signalling efficiency between the L-type Ca 2+ channels (LCCs) in the plasma membrane (including transverse tubules, TTs) and the ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) underlies the defective excitation -contraction (E-C) coupling. It is therefore intriguing to know how the LCC -RyR signalling apparatus is remodelled in human heart failure. Methods and resultsStereological analysis of transmission electron microscopic images showed that the volume densities and the surface areas of TTs and junctional SRs were both decreased in heart failure specimens of dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). The TT-SR junctions were reduced by 60%, with the remaining displaced from the Z-line areas. Moreover, the spatial span of individual TT -SR junctions was reduced by 17% in both DCM and ICM tissues. In accordance with these remodelling, junctophilin-2 (JP2), a structural protein anchoring SRs to TTs, was down-regulated, and miR-24, a microRNA that suppresses JP2 expression, was up-regulated in both heart failure tissues. ConclusionHuman heart failure of distinct causes shared similar physical uncoupling between TTs and SRs, which appeared attributable to the reduced expression of JP2 and increased expression of miR-24. Therapeutic strategy against JP2 down-regulation would be expected to protect patients from cardiac

show abstract

“…Quantitative changes in cellular constitutents are characterized by a decrease in the volume ratio: mitochondridmyofibrils (Lund and Tomanek, 1978;Tomanek et al, 1979;Tomanek, 1979a,b;Tomanek and Hovanec, 1981). A decrease in this ratio due to a relative increase in myofibrillar volume and/or a relative decrease in mitochodrial volume has also been found in other forms of pressure overload, i.e., aortic constriction (Page et al, 1972;Goldstein et al, 1974;Anversa et al, 1976;Lund and Tomanek, 1978) and renal artery constriction (Wiener et al, 1979;Wendt-Gallitelli and Jacob, 1977). Such a decrement in the ratio of energy-producing to energy-consuming organelles could presumably limit myocardial metabolism under conditions requiring high 0 2 utilization.…”

mentioning

confidence: 95%

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats

Lauva

Tomanek

1983

Anat. Rec.

View full text Add to dashboard Cite

In this study we investigated the effects of chronic beta adrenoreceptor blockade with atenolol on cellular and subcellular hypertrophy in spontaneously hypertensive rats (SHR). Atenolol was injected subcutaneously (20 mg/kg) twice daily commencing in four-week-old rats. The treated animals (SHR-A) were compared to their nontreated controls and normotensive, Wistar-Kyoto (WKY) controls at the age of 16 weeks. A group of atenolol-treated WKY was also studied. Chronic drug treatment was effective in attenuating the rise in systolic blood pressure characteristic of SHR, but did not normalize the values to those of WKY. Cardiac hypertrophy, characteristic of SHR, was modified by drug treatment as evidenced by left ventricular weights as well as myocardial cell size. The cells from the subendocardium underwent selective hypertrophy in SHR which was attenuated by about 50% after atenolol treatment. Stereological analysis of electron micrographs showed that while relative mitochondrial volume was not affected by treatment, relative myofibrillar volume (%) decreased in both subepicardium (SHR = 63.28 +/- 1.25; SHR-A = 56.72 +/- 1.37) and subendocardium (SHR = 66.53 +/- 1.27; SHR-A = 58.30 +/- 1.51). This change raised the mitochondrial/myofibrillar volume ratio, which is characteristically low in SHR compared to WKY. Sarcoplasm, which included all cell constituents except mitochondria, increased with atenolol treatment, but water concentration remained unchanged. The data suggest that attenuation of hypertrophy in SHR after beta blockade is associated with selective effects on the myocardial cell involving primarily the myofibrillar cell compartment.

show abstract

Time course of electron microscopic alterations in the hypertrophied myocardium of Goldblatt rats

Cited by 20 publications

References 4 publications

Effects of spermine on mitochondrial Ca2+ transport and the ranges of extramitochondrial Ca2+ to which the matrix Ca2+-sensitive dehydrogenases respond

Effects of spermine on mitochondrial Ca2+ transport and the ranges of extramitochondrial Ca2+ to which the matrix Ca2+-sensitive dehydrogenases respond

Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats

Contact Info

Product

Resources

About