Studies of sarcoplasmic reticulum function and contraction duration in young adult and aged rat myocardium

Froehlich, Jeffrey P.; Lakatta, Edward G.; Beard, Elsie S.; Spurgeon, Harold A.; Weisfeldt, Myron L.; Gerstenblith, Gary

doi:10.1016/0022-2828(78)90364-4

Cited by 190 publications

(84 citation statements)

References 34 publications

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“…Similarly, in aged rat hearts reduced SERCA2 expression and activity was demonstrated (Buttrick et al, 1991;Froehlich et al, 1978;Lompre et al, 1991). Li et al (2007) recently reported reduced SERCA2 expression and activity in aged hearts of FVB mice, whereas we previously showed diastolic dysfunction in aged ventricular myocytes of C57BL/6 mice without changes in protein expression of SERCA2 .…”

Section: Introductionmentioning

confidence: 51%

NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

Rueckschloss

Villmow

Klöckner

2010

Experimental Gerontology

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractSince aging increases oxidative stress, we analyzed the contribution of reactive oxygen species (ROS) to the contractile dysfunction of aged ventricular myocytes and investigated whether short-term interference with ROS formation could normalize contractile performance.Isolated ventricular myocytes from young (2-4 months) and aged (24-26 months) male mice (C57BL/6) were used. We analyzed sarcomere shortening and calcium transients We found that aged myocytes showed decelerated shortening/ relengthening without changes in fractional shortening. Calcium transient decay was similarly decelerated, but the amplitude of calcium transients was increased with aging. Calcium sensitivity of myofilaments of aged myocytes was reduced. These age-dependent changes occurred without altered calcium handling protein expression but were reversed by the superoxide scavenger tiron. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPTAged myocytes showed increased NADPH oxidase expression and activity.Pharmacological inhibition of NADPH oxidase (diphenylene iodonium; apocynin) normalized age-dependent deceleration of shortening/ relengthening.In summary, we show that increased superoxide formation by upregulated NADPH oxidase contributes significantly to age-dependent alterations in calcium handling and contractility of murine ventricular myocytes.

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Section: Introductionmentioning

confidence: 51%

NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

Rueckschloss

Villmow

Klöckner

2010

Experimental Gerontology

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“…Expression of mRNAs encoding the SR Ca2+-ATPase and cardiac calsequestrin in the rat LV myocardium. RNA blot hybridization was carried out with cDNA clones specific for the rabbit cardiac-slow twitch skeletal SR Ca2+-ATPase (27) and canine cardiac calsequestrin (25). The SR Ca2+-ATPase cDNA probe (pCA) hybridized with an mRNA species of -4 kb.…”

Section: Resultsmentioning

confidence: 99%

“…The prolongation of myocardial contraction has been attributed to a decline ofCa2+-activated myosin-ATPase activity, secondary to a decrease in the percentage of a-MHC or V1 isozyme (25,26). The abnormal myocardial relaxation has been thought to reflect age-related decreases in Ca2+-uptake by the SR (27,28).…”

Section: Introductionmentioning

confidence: 99%

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

Takahashi¹,

Schunkert²,

Isoyama³

et al. 1992

J. Clin. Invest.

143

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IntroductionCardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression ofc-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of,-to a-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca2"-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal a-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac a-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress. (J. Clin. Invest. 1992. 89:939-946.) Key words: actin . myosin heavy chain * calsequestrin * Ca2+-ATPase -atrial natriuretic factor

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“…57 The prolonged Ca i that occurs with aging is explained, in part, by a reduction in the rate of Ca 2ϩ sequestration by the sarcoplasmic reticulum ( Figure 2D). 58 This is attributable to a reduced transcription of the gene coding for the sarcoplasmic reticulum Ca 2ϩ pump, SERCA2 (see 59 for review). The abundance of transcripts of the cardiac Na ϩ -Ca 2ϩ exchanger (NCX-1), which serves as the main trans-sarcolemmal Ca 2ϩ extrusion mechanism, is increased Ϸ50% in senescent (24-month) compared with the young adult (6-month) rat hearts.…”

Section: Links Between Arterial Aging and Atherosclerosismentioning

confidence: 99%

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

2003

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Studies of sarcoplasmic reticulum function and contraction duration in young adult and aged rat myocardium

Cited by 190 publications

References 34 publications

NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

NADPH oxidase-derived superoxide impairs calcium transients and contraction in aged murine ventricular myocytes

Age-related differences in the expression of proto-oncogene and contractile protein genes in response to pressure overload in the rat myocardium.

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

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