Mechanical stress-dependent transcriptional regulation of sarcolipin gene in the rodent atrium

Shimura, Miei; Minamisawa, Susumu; Yokoyama, Utako; Umemura, Satoshi; Ishikawa, Yoshihiro

doi:10.1016/j.bbrc.2005.06.186

Cited by 18 publications

(20 citation statements)

References 24 publications

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“…The role of SLN expression in PAB animals is less understood. Recently, Shimura et al (41) showed that SLN mRNA was downregulated in the atrial myocardium of mice due to pressure overload. Currently, there are no protein data available to validate the importance of SLN in PAB rabbits.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary artery banding alters the expression of Ca²⁺transport proteins in the right atrium in rabbits

Gupta¹,

Varian²,

Bal³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Subsequently, the right atrium (RA) has to contract against a higher afterload, but it is unknown to what extent ventricular dysfunction has an effect on the atrial contractility. We hypothesized that right ventricular pressure overload may have an affect on atrial contractility and Ca 2ϩ transport protein expression. Therefore, we induced pressure overload of the right ventricle by PAB for 10 wk in rabbits and examined the changes in the expression of Ca 2ϩ transport proteins in the atrium. We demonstrate that PAB significantly decreased the expression of sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (Serca) 2a while expression of Na ϩ /Ca 2ϩ exchanger-1 was significantly upregulated in the RA but not in the left atria of rabbit hearts, indicating that pressure is the major trigger. A decrease in Serca2a expression was concomitant with a significant decrease in sarcolipin (SLN), possibly indicating a compensatory role of SLN. The decreased expression of SLN was unable to completely restore sarcoplasmic reticulum Ca 2ϩ uptake function of Serca2a. Functional contractile assessments in isolated trabeculae showed no difference between PAB-and sham-operated rabbits at 1 Hz but displayed an enhanced force development at higher frequencies and in the presence of isoproterenol, while twitch timing was unaffected. Our results indicate that right ventricular mechanical overload due to PAB affects the expression of the Ca 2ϩ -handling proteins in the RA in rabbits.calcium ion transport proteins; pressure overload; sarcoplasmic reticulum

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Section: Discussionmentioning

confidence: 99%

Pulmonary artery banding alters the expression of Ca²⁺transport proteins in the right atrium in rabbits

Gupta¹,

Varian²,

Bal³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Recent studies showed that SLN mRNA is down-regulated in atrial myocardium of patients with chronic atrial fibrillation [12] and in the atria of pressure overloaded hypertrophy [13]. However, there are no protein data available to date to validate the importance of SLN in cardiac pathology.…”

Section: Discussionmentioning

confidence: 99%

“…Pressure-overloaded hypertrophy induced by transverse aortic constriction in mice or by monocrotaline administration in rats significantly decreased the expression of SLN, SERCA2a, and phospholamban mRNAs in the atrium [13]. In human, decreased expression of SLN mRNA has been reported in the atria of patients with atrial fibrillation [12].…”

Section: Introductionmentioning

confidence: 96%

“…SLN mRNA expression is shown to be developmentally regulated [4,5] and is altered by thyroid hormones [9,10] and pathophysiological conditions [3,4,[11][12][13]. Pressure-overloaded hypertrophy induced by transverse aortic constriction in mice or by monocrotaline administration in rats significantly decreased the expression of SLN, SERCA2a, and phospholamban mRNAs in the atrium [13].…”

Section: Introductionmentioning

confidence: 99%

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Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology

Babu¹,

Bhupathy²,

Carnes³

et al. 2007

Journal of Molecular and Cellular Cardiology

129

150

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Sarcolipin (SLN) is a small molecular weight sarcoplasmic reticulum (SR) membrane protein expressed both in cardiac and skeletal muscle tissues. Recent studies using transgenic mouse models have demonstrated that SLN is an important regulator of cardiac SR Ca 2+ ATPase 2a (SERCA2a). However, there is a paucity of information regarding the SLN protein expression in small versus larger mammals and its regulation during development and cardiac pathophysiology. Therefore, the major goal of this study was to generate a SLN specific antibody and perform detailed analyses of SLN protein expression during muscle development and in the diseased myocardium. The important findings of the present study are: (i) in small mammals, SLN expression is predominant in the atria but low in the ventricle and in skeletal muscle tissues, whereas in large mammals, SLN is quite abundant in skeletal muscle tissues than the atria (ii) SLN and SERCA2a are co-expressed in all striated muscle tissues studied except ventricle and co-ordinately regulated during muscle development and (iii) SLN protein levels are ∼3 fold upregulated in the atria of heart failure dogs and ∼30% decreased in the atria of hearts prone to myocardial ischemia. In addition we found that in the phospholamban null atria, SLN protein levels are upregulated.

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“…SLN expression is regulated during cardiac and skeletal muscle development (2)(3)(4). Furthermore, SLN expression levels are altered in atria during cardiac pathology both in animal models (2,4,(11)(12)(13) and in humans (14), suggesting that SLN levels may play an important role in maintaining atrial Ca 2ϩ homeostasis during cardiac pathophysiology.…”

mentioning

confidence: 99%

Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility

Babu

Bhupathy

Timofeyev

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

118

112

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Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca 2؉ ATPase 2a (SERCA2a) and is expressed abundantly in atria. In this study we investigated the physiological significance of sarcolipin in the heart by generating a mouse model deficient for sarcolipin. The sarcolipin-null mice do not show any developmental abnormalities or any cardiac pathology. The absence of sarcolipin does not modify the expression level of other Ca 2؉ handling proteins, in particular phospholamban, and its phosphorylation status. Calcium uptake studies revealed that, in the atria, ablation of sarcolipin resulted in an increase in the affinity of the SERCA pump for Ca 2؉ and the maximum velocity of Ca 2؉ uptake rates. An important finding is that ablation of sarcolipin resulted in an increase in atrial Ca 2؉ transient amplitudes, and this resulted in enhanced atrial contractility. Furthermore, atria from sarcolipinnull mice showed a blunted response to isoproterenol stimulation, implicating sarcolipin as a mediator of ␤-adrenergic responses in atria. Our study documented that sarcolipin is a key regulator of SERCA2a in atria. Importantly, our data demonstrate the existence of distinct modulators for the SERCA pump in the atria and ventricles.atria ͉ calcium uptake ͉ sarcoplasmic reticulum Ca 2ϩ ATPase 2 S arcolipin (SLN), a low-molecular-weight protein (31 aa), is expressed in both cardiac and skeletal muscles (1-5). It colocalizes with sarcoplasmic reticulum (SR) Ca 2ϩ ATPase (SERCA) in the cardiac SR (3) and physically interacts with the SERCA pump (6). Amino acid composition and structural analysis have suggested that SLN and phospholamban (PLB) may belong to the same family of proteins with similar functions (1,(7)(8)(9). Consistent with the notion, in vitro studies have shown that SLN can inhibit the SERCA activity by decreasing the apparent Ca 2ϩ affinity of the pump (7, 10). Protein expression analyses have demonstrated that within the heart there are chamber-specific differences in the expression pattern of SLN and PLB (4). SLN is predominantly expressed in the atrial compartment, whereas PLB is abundant in the ventricles. In addition to atria, SLN is expressed in skeletal muscle tissues (4). SLN expression is regulated during cardiac and skeletal muscle development (2-4). Furthermore, SLN expression levels are altered in atria during cardiac pathology both in animal models (2, 4, 11-13) and in humans (14), suggesting that SLN levels may play an important role in maintaining atrial Ca 2ϩ homeostasis during cardiac pathophysiology.The importance of SLN as a regulator of the cardiac SERCA pump was recently demonstrated by using adenoviral gene transfer into adult rat ventricular myocytes (3) and transgenic overexpression of SLN in the heart (15-17). These studies suggest that overexpression of SLN into ventricular myocytes resulted in decreased rates of SR Ca 2ϩ uptake, Ca 2ϩ transient amplitude, and myocyte contractility. Overexpression of SLN in the PLB-null heart revealed that SLN can inhibit SERCA pump activity in...

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Mechanical stress-dependent transcriptional regulation of sarcolipin gene in the rodent atrium

Cited by 18 publications

References 24 publications

Pulmonary artery banding alters the expression of Ca²⁺transport proteins in the right atrium in rabbits

Pulmonary artery banding alters the expression of Ca²⁺transport proteins in the right atrium in rabbits

Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology

Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility

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Mechanical stress-dependent transcriptional regulation of sarcolipin gene in the rodent atrium

Cited by 18 publications

References 24 publications

Pulmonary artery banding alters the expression of Ca2+transport proteins in the right atrium in rabbits

Pulmonary artery banding alters the expression of Ca2+transport proteins in the right atrium in rabbits

Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology

Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility

Contact Info

Product

Resources

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Pulmonary artery banding alters the expression of Ca²⁺transport proteins in the right atrium in rabbits

Pulmonary artery banding alters the expression of Ca²⁺transport proteins in the right atrium in rabbits