From the Department of Pediatric Cardiology and the
§§ Division of Genomic Medicine, Institute of Advanced
Biomedical Engineering and Science, Graduate School of Medicine, Tokyo
Women's Medical University, Tokyo 162-8666, Japan, the
§ Department of Physiology, Yokohama City University School
of Medicine, Yokohama, 236-0004 Japan, the
Department of
Physiology, University of Maryland School of Medicine, Baltimore,
Maryland 21201, the ** Institute of Molecular Medicine,
University of California at San Diego, La Jolla, California 92093, and the
Department of Cell Biology and Molecular
Medicine, New Jersey Medical School, Newark, New Jersey 07103
Received for publication, December 23, 2002
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Intracellular Ca2+ regulation
is critical in the normal cardiac function and development of
pathologic hearts. Phospholamban, an endogenous inhibitor of
sarcoplasmic reticulum Ca2+ ATPase in the sarcoplasmic
reticulum, plays an important role in Ca2+ cycling in
heart. Recently, sarcolipin has been identified as having a similar
function as phospholamban in skeletal muscle. Because phospholamban is
differentially expressed in atrial and ventricular myocardia and its
expression is often altered in diseased hearts, we investigated the
cardiac chamber specificity of sarcolipin expression and its regulation
during development and hypertrophic remodeling. Northern blot analysis
revealed that the expression of mouse sarcolipin mRNA was most
abundant in the atria and was undetectable in the ventricles,
indicating an atrial chamber-specific expression pattern. Atrial
chamber-specific expression of sarcolipin mRNA was increased during
development. These findings were confirmed by in situ
hybridization studies. In addition, sarcolipin expression was
down-regulated in the atria of hypertrophic heart when induced by
ventricular specific overexpression of the activated
H-ras gene. In humans, sarcolipin mRNA was
also expressed in the atria but not detected in the ventricles,
although sarcolipin expression was most abundant in skeletal muscle.
Taken together, sarcolipin is likely to be an atrial chamber-specific
regulator of Ca2+ cycling in heart.
Sarcolipin (SLN)1 is a
31-amino acid proteolipid in the sarcoplasmic reticulum (SR) (1) and is
shown to be expressed most abundantly in fast twitch skeletal muscle,
less abundantly in slow twitch skeletal muscle, and even less in human
and rabbit cardiac muscle (2). This tissue distribution corresponds to that of the fast twitch skeletal muscle SR Ca2+ ATPase
(SERCA1), and SLN interacts with SERCA1 to modulate its activity (3,
4). By contrast, phospholamban (PLN), an integral membrane protein in
the SR, is expressed abundantly in cardiac and slow twitch skeletal
muscle wherein SERCA2a is the predominant SERCA isoform (5). Thus, SLN
expression is complementary to PLN expression. The structure and
protein sequence of SLN are similar to those of PLN (2). Therefore, SLN
and PLN may belong to the same family, and SLN is likely to be an
analog of PLN in skeletal muscle.
PLN is an endogenous inhibitor of SERCA2 and plays a central role in
regulating cardiac contractility and relaxation (6, 7). Studies using
gene-targeted mice have revealed that disruption of the PLN gene can
prevent the progression of cardiomyopathy (8, 9), suggesting that PLN
plays a critical role in the development of heart failure. The
expression of PLN is regulated by developmental, hormonal, and
hemodynamic changes (7). In the heart, PLN is expressed predominantly
in the ventricles and, to a lesser extent, in the atria (10). The
different levels of PLN expression in the heart are, in part,
responsible for the differences in the contractile properties between
the atria and the ventricles.
In contrast to PLN, the role of SLN in the heart remains unknown, even
though SLN may play an important role in skeletal muscle contraction
(11). Because SLN expression is complementary to PLN expression, we
hypothesize that SLN expression in the heart is higher in the atria and
is regulated in a developmental stage-specific manner and/or by cardiac
stress. In addition, Asahi et al. (4) demonstrated recently
that SLN inhibited polymerization of PLN, resulting in the
superinhibition of SERCA1 and SERCA2a. Therefore, characterizing the
expression pattern of SLN is important for establishing the potential
modulatory role in cardiac function.
In the present study, we examined the effects of development and
cardiac hypertrophy on the expression of SLN mRNA in heart. We
found that the expression of SLN mRNA was detected selectively in
the atria. Furthermore, SLN was up-regulated during development and
down-regulated by cardiac hypertrophy. SLN mRNA remained
undetectable in the ventricles during development or in the
hypertrophic state, indicating that the atrial chamber-specificity of
SLN was conserved. Taken together, we propose that SLN may serve an
important regulator of Ca2+ cycling in the atrium and may
be an important factor in differentiating the contractile properties of
the atria from those of the ventricles.
Animals and Tissue Samples--
ICR mice obtained from Clea
Japan Inc. (Tokyo, Japan) were inbred at Tokyo Women's Medical
University. Embryos from ICR mice were obtained from timed pregnant animals.
The transgenic model of cardiac hypertrophy was established by
ventricular specific expression of activated H-ras
transgene. In this study, we applied the same "gene-switch"
transgenic strategy as reported previously (12). Briefly, a green
fluorescence protein (GFP) coding sequence and poly(A) regions were
cloned from pEGFP-N1 (Invitrogen) and inserted between the two
loxP sequences of the pUC1015loxlox vector (a gift from Dr. Jamy Marth,
University of California, San Diego, CA) to generate the pfloxGFP
vector. The XbaI/SmaI fragment from pfloxGFP,
containing the GFP-poly(A) sequences flanked by two copies of loxP, was
then inserted at the HindIII site of the pMHC vector behind
the 5.5 kilobase mouse
Human tissues were obtained from specimens at autopsy. Informed consent
was obtained from the patients and/or their families.
Total RNA Isolation--
Total RNA was isolated from various
tissues using TRIzol reagent (Invitrogen) as recommended by the
manufacturer. For the developmental study, atrial and left ventricular
tissues from embryos and neonates were pooled. The isolated RNA was
quantified by spectrophotometry.
cDNA and RNA Probes--
To obtain the mouse and human
full-length SLN cDNAs and mouse partial-length SERCA1 cDNA,
a set of primers was designed based on the reported sequence
(Table I). The mouse SERCA1 cDNA
included the end of the coding sequence and 3'-untranslated
region. Reverse transcription PCR was performed using the
Superscript preamplification system (Invitrogen) as recommended by the
manufacturer. The reaction of PCR was set to denature at 94 °C for
30 s, anneal at 55 °C for 30 s, and extend at 72 °C for
45 s for 30 cycles. The obtained PCR fragments were subcloned in
pCR II vector (Invitrogen). The antisense mouse SLN digoxygenin-labeled
RNA probe was created from 1 µg of HindIII-linearized
mouse SLN pCRII vector using T3 RNA polymerase.
Mouse SERCA2a and PLN cDNA probes were kindly provided by Dr.
Wolfgang H. Dillmann (University of California, San Diego, CA) and Dr.
Evangelia G. Kranias (University of Cincinnati College of Medicine),
respectively. We confirmed the nucleotide sequences of these probes
compared with the reported sequences by direct DNA sequencing.
Northern Blot Analysis--
Northern blot analysis was performed
as described previously with modification (14). Total RNA was
electrophoresed on a 1% formaldehyde-agarose gel and transferred onto
Nytran membranes (Schleicher & Schuell). Blots were hybridized at
68 °C with radiolabeled probes in Quickhyb solution (Stratagene, La
Jolla, CA) as recommended by the manufacturer. Membranes were washed
under high stringency conditions (0.1× SSC, 0.1% SDS) at
60 °C.
In Situ Hybridization--
In situ
hybridization was performed as described previously (15). Paraffin
sections were prepared using a standard protocol.
SERCA Activity--
Microsomes enriched in SR membranes were
obtained as described previously (16). SR Ca2+ ATPase
activity was measured as described previously with modification (17).
Using 5 µg of SR protein, the reaction was carried out at 37 °C in
the reaction medium containing 30 mM TES, 100 mM KCl, 5 mM NaN3, 5 mM
MgCl2, 0.5 mM EGTA, and 4 mM ATP
with or without 0.5 CaCl2. Data are expressed as mean ± S.E. Statistical significance was analyzed using Student's unpaired
t test.
SLN mRNA Was Expressed Abundantly in the Murine Atria--
The
distribution of SLN mRNA in various mouse tissues was analyzed by
Northern blot using a PCR-amplified cDNA probe as described under
"Experimental Procedures." A single 0.9-kb transcript was detected.
Specifically, SLN mRNA expression was most abundant in the atria of
the heart, less abundant in esophageal muscle, and least abundant in
skeletal muscle and bladder (Fig.
1A). In murine myocardium, the
expression of SLN mRNA was restricted to the atria and was not
present in the ventricles. In skeletal muscle, the similar level of SLN
mRNA expression was detected in fast twitch skeletal muscle
(extensor digitorum longus muscle) and slow twitch skeletal muscle
(soleus muscle). In smooth muscle, SLN mRNA expression was much
greater in esophagus than in bladder. SLN mRNA was not detected in
brain, kidney, liver, spleen, thymus, and lung (liver, spleen, thymus,
and lung, data not shown) by Northern blot analysis.
In situ hybridization analysis using an antisense SLN RNA
probe also demonstrated that SLN mRNA was expressed only in the atria and not in the ventricles of the heart (Fig. 1B). The
localization of SLN transcript was distributed uniformly in both right
and left atria.
We also examined the expression of SERCA1 mRNA in the mouse heart,
because SLN is believed to interact with SERCA1. As shown in Fig.
1A, a very small amount of the SERCA1 transcript was
detected in the atria. The level of SERCA2 mRNA in the atria was
comparable with that in the ventricles. At the protein level, only
SERCA2a but not SERCA1 was detected in the atria, using SERCA
isoform-specific antibodies (data not shown; SERCA1 antibody (MA3-912)
and SERCA2 antibody (MA3-919) were from Affinity Bioreagents, Inc.).
There was abundant SERCA1 expression in mouse smooth muscle. SERCA1 mRNA levels were similar in esophagus and bladder. The tissue distribution of PLN and SERCA2a was consistent with previous reports (18, 19). SR Ca2+ ATPase activity in the atria
(n = 5) was significantly higher than that in the
ventricles (n = 7) (1573 ± 85 nmol/mg of
protein/min and 348 ± 35 nmol/mg of protein/min, respectively) in
adult murine hearts.
SLN Was Developmentally Up-regulated in the Atria--
The
developmental changes of SLN and SERCA1 mRNA in the atria were also
determined by Northern blot analysis. Fig.
2A demonstrates that the
expression of SLN and SERCA1 mRNA was increased over time in the
atria and not detected in the ventricles at any of the developmental
stages. Interestingly, the expression of SERCA1 mRNA became very
low in the atria in older mice (2 years old), suggesting that SERCA1
expression is down-regulated in the atria with aging. The expression of
ANF transcript was also increased over time in the atria. In contrast
to SLN, ANF transcripts were detected in the ventricles of embryos at
embryonic day 17.5 and at 2 years old of age. We further examined the
developmental changes of SLN and SERCA1 mRNA expression in detail.
No SLN transcript was found in embryos at embryonic day 10.5 but became
detectable in the atria at embryonic day 12.5 (Fig. 2B).
After embryonic day 16.5, the expression of SLN mRNA was abruptly
increased in the atria. These changes were confirmed by in
situ hybridization studies using embryos at specific developmental
stages. At embryonic day 9.5 no SLN transcript was detected (data not
shown), whereas at embryonic day 12.5 SLN mRNA was present at a low
level in the atria and expressed abundantly in the progenitors of
skeletal muscle (Fig. 3).
SERCA1 mRNA was expressed weakly in the atria at embryonic day 10.5 and 12.5 but was not detectable after embryonic day 16.5 (Fig.
2B). The SERCA1 transcript was detected again at 21 days after birth. Thus, the developmental changes in SLN and SERCA1 transcripts were not exactly coordinated.
SLN and SERCA1 mRNA Were Down-regulated in the Atria in
Hypertrophic Hearts--
The transgenic mice overexpressing activated
H-ras developed severe concentric ventricular hypertrophy
with concomitant obstruction of forward blood flow from the atria to
the ventricles, resulting in marked enlargement of atrial chambers
(Fig. 4). The levels of SLN, PLN, SERCA1
and SERCA2a mRNA were all decreased in the atria of the transgenic
mice at 3 months old (Fig. 5). Although ANF and BNP transcripts were increased in both the atria and ventricles of the transgenic mice, SLN mRNA remained undetectable in the hypertrophic ventricles.
SLN mRNA Was Also Expressed Specifically in the Human
Atria--
Although a previous study showed that SLN expression was
low in human heart, its chamber-specific localization has remained undetermined. We found that SLN mRNA was expressed abundantly in
human atria and was undetectable in ventricles (Fig.
6). In contrast to mouse, the expression
of SLN in the atria was lower than in skeletal muscle in human. Using
the mouse SERCA1 cDNA probe that has 75% homology with human
SERCA1, no hybridization signal was detected in the human atria, even
under low stringent conditions.
The present study revealed that SLN mRNA was expressed
abundantly in the murine and human atria but was not detected in the murine and human ventricles by Northern blot analysis. In mice, the
expression of SLN mRNA was most abundant in the atria, and it was
lower in skeletal muscle than in the atria and smooth muscle. By
contrast, in humans the expression of SLN mRNA was weaker in the
atria than that in skeletal muscle. Previous studies have demonstrated
the predominant expression of SLN mRNA in human and rabbit fast
skeletal muscle (2) and the very weak expression of SLN mRNA in rat
extensor digitorum longus (EDL) muscle (20). These data are consistent
with the findings in the present study, suggesting that the tissue
distribution of sarcolipin mRNA is regulated differently between
humans and rodents. The fact that the nucleotide sequence of SLN
cDNA is not well conserved between mice and humans and that their
polyadenylation signal sequences are different (2) may account for the
different tissue distribution between rodents and humans.
Importantly, the atrial chamber-specific expression of SLN was
developmentally up-regulated, and it was down-regulated in hypertrophic
remodeling at the transcriptional level. These changes are similar to
those of PLN in the ventricles (21) (22). No ventricular SLN expression
was detected at any stage of development or cardiac hypertrophy. We did
not investigate the protein levels of SLN, because a SLN antibody was
not readily available. However, a previous study (2) demonstrated that
changes in the SLN levels of mRNA and protein are proportional,
although the magnitude of the changes in SLN protein was greater than
that in SLN mRNA in the skeletal muscle. Therefore, it is likely
that the SLN protein is also expressed abundantly in the murine atria.
PLN decreases the apparent affinity of SERCA2a for Ca2+ and
inhibits Ca2+ uptake into the SR. The expression level of
PLN directly affects cardiac contractility and relaxation in the heart
(23, 24). SLN also inhibits Ca2+ uptake at low
Ca2+ concentrations like PLN but enhances Ca2+
uptake at high Ca2+ concentrations (3, 25). Therefore, the
atrial chamber-specific expression of SLN may be related to functional
differences between the atria and ventricles, and the abundant
expression of SLN may play an important role in the regulation of
Ca2+ cycling in the atrial myocardium.
The coordinated contraction of the atria with the ventricles is
essential for normal cardiac output. However, the physiological characteristics are quite different between atrial and ventricular myocardium. For examples, muscle contraction time, measured as a time
to peak tension, and the duration of the myocyte Ca2+
transients are shorter in atrial muscle compared with ventricular muscle. In the present study, we also found that SR Ca2+
ATPase activity is significantly higher in the atria than in the
ventricles. This may be due to different levels of PLN expression between atria and ventricles (10). In addition to the lower expression
of PLN, SLN may also contribute to the chamber-specific physiological
properties of the atria. Furthermore, we found that SERCA1 mRNA was
expressed weakly in the mouse atria and that its expression was also
regulated during development and hypertrophic remodeling. However, it
is unlikely that SERCA1 contributes to the higher ATPase activity in
the atria, because SERCA2a is the predominant isoform, and the SERCA1
protein was not detected in the atria.
In skeletal muscle, SLN expression is regulated by chronic low
frequency stimulation (3) or corticosteroids (20). Odermatt et
al. (3) suggested that reduced SLN expression associated with the
decrease in SERCA1 activity represented an early functional adaptation
to chronic low frequency stimulation. They proposed that SLN provides a
constant stimulation of SERCA Vmax to increase the activity of SERCA. Thus, the abundant expression of SLN with an
increase in the activity of SERCA and faster contraction in the atria
is consistent with this model. However, these investigators demonstrated recently that SLN inhibited both SERCA1 and SERCA2a activities in human embryonic kidney 293 cells (4) and in in vivo slow skeletal muscle (11). Moreover, they suggested that SLN
binds directly to PLN and increases the formation of PLN monomers that
inhibits SERCA activity (4). If these data are true in the in
vivo heart, overexpression of SLN should result in the depression
of SERCA activity and slow muscle contraction. Further studies using
transgenic mice overexpressing SLN in heart are needed to address these issues.
Using a Ras transgenic mouse model for hypertrophy, we demonstrated
that SLN mRNA was down-regulated in cardiac hypertrophy. Isolated
cardiomyocytes from Ras transgenic mice displayed reduced contraction
and prolonged Ca2+ transients compared with wild-type
myocytes2 despite the
reduction of PLN expression. Other studies also demonstrated that Ca2+ cycling in the atria is impaired in cardiac
hypertrophy or chronic atrial stimulation such as atrial fibrillation.
Therefore, decreases in the expression of SLN, SERCA1, and SERCA2 may
result in the reduction of Ca2+ uptake in the atria and may
play a more important role in maintaining the atrial function than the
level of PLN expression.
Another important finding in the present study is that SLN mRNA was
not expressed in the ventricular myocardium during any stage of
development or in a cardiac hypertrophic state, indicating that SLN is
an atrial chamber-specific molecular marker. In contrast to SLN, other
atrial chamber-specific molecular markers such as ANF and atrial type
of myosin light chain 1 are induced in ventricles by cardiac stresses.
Therefore, a putative promoter/enhancer gene fragment of SLN may be
useful for atrial chamber-specific gene targeting or gene delivery.
In conclusion, we found that SLN, a counterpart of PLN, was expressed
specifically in the atrial myocardium. The atrial chamber-specific expression of SLN was up-regulated during development and
down-regulated in hypertrophic remodeling. The present study suggests
that SLN is an important regulator of Ca2+ cycling in the atrium.
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
EXPERIMENTAL PROCEDURES
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
-MHC promoter (a gift from Dr. Jeffery
Robbins, University of Cincinnati) to generate the
pMHC-floxGFP vector. The cDNA fragment coding for the activated
H-ras (V15) mutant was then inserted at the EcoRV site behind the loxP-GFP-loxP fragment to generate the final
pMHC-floxRas vector. Transgenic mice (floxRas) were generated by
established intra-nuclear injection methods using a
KpnI/SstI fragment digested from the pMHC-floxRas
vector. The GFP marker gene was expressed in both the atria and
ventricles. The floxRas mice were crossed with MLC-2v/Cre mice in which
the Cre enzyme was only expressed in the ventricular muscle cells. The
GFP expression cassette was floxed out, and the activated
H-ras mutant was led to be expressed in the ventricles of
double transgenic mice. The effect of the H-ras mutant on
cardiac hypertrophy has been validated (13).
Primers
RESULTS
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
View larger version (41K):
[in a new window]
Fig. 1.
Atrial chamber-specific expression of
sarcolipin mRNA. A, northern blot analysis for
the various mouse tissues. Using the full-length SLN cDNA probe, a
single transcript of 0.9 kb was expressed most abundantly in the atria
of the heart, less abundantly in esophageal muscle, and least
abundantly in skeletal muscle and bladder. No hybridized signal was
detected in the ventricles. A small amount of SERCA1 transcript was
detected in the atria. There was robust SERCA1 expression in mouse
smooth muscle. Glyceraldehyde-3-phosphate dehydrogenase
(GAPDH) was used for internal control. B,
in situ hybridization analysis using an antisense SLN RNA
probe. SLN mRNA was expressed restrictedly in the atria but not in
the ventricles. The localization of SLN transcript was distributed
uniformly in both the right and left atria. C, a high
magnification image of the lesion indicated as a rectangle
in panel B. EDL, extensor digitorum
longus muscle; LV, left ventricle; RV, right
ventricle; LA, left atrium; RA, right atrium.
Bar, 1 mm (B).
View larger version (39K):
[in a new window]
Fig. 2.
Developmental up-regulation of sarcolipin
mRNA in the atria. A, the developmental change in
the expression of SLN, SERCA1, and ANF mRNA in the atrial and
ventricular myocardium. Northern blot analysis revealed that these
transcripts are up-regulated during development in the atria. The
expression of ANF transcript was also detected in the ventricles of
embryos at embryonic day 17.5 and in older mice (at 2 years old).
B, the developmental changes in the atrial expression of SLN
and SERCA1 mRNA in detail. No SLN transcript was detected in
embryos at embryonic day (ed) 10.5 but became detectable in
the atria at embryonic day 12.5. After embryonic day 16.5, the
expression of SLN mRNA was abruptly increased.
View larger version (86K):
[in a new window]
Fig. 3.
In situ hybridization analysis of
sarcolipin mRNA in an embryo at embryonic day 12.5. Using an
antisense SLN riboprobe, SLN mRNA was detected at low levels in the
atria and was much higher in the progenitors of skeletal muscle.
A, atrium; L, liver; T, tongue;
V, ventricle. Bar, 1 mm.
View larger version (66K):
[in a new window]
Fig. 4.
Marked ventricular hypertrophy and dilated
atria in Ras transgenic mice. The activated H-ras
transgenic mice developed severe concentric ventricular hypertrophy and
marked enlargement of atrial chambers (A, B, and
C, non-transgenic mice; D, E,
F, and H, activated H-ras transgenic
mice). Panels A and D are the
cross-sections of the ventricles. Severe concentric ventricular
hypertrophy was detected in the activated H-ras transgenic
mice (D). Panel E is a high
magnification image of the left ventricle of the activated
H-ras transgenic mice demonstrating disorganized myofibrils.
Organized thrombi were found frequently in the atria of the activated
H-ras transgenic mice (panels F and
H). Panel H is the frontal section of
a H-ras transgenic heart.
View larger version (54K):
[in a new window]
Fig. 5.
Down-regulation of sarcolipin and SERCA1
mRNA in H-ras transgenic mice. The
representative Northern blot analysis of the activated H-ras
transgenic mice. The expressions of SLN, PLN, SERCA1, and SERCA2a
mRNA were all down-regulated in the atria of the H-ras
transgenic mice at 3 months old. ANF and BNP were induced in the atria
and the ventricles of the H-ras transgenic mice.
RasTG, the activated H-ras transgenic mice;
NTG, non-transgenic mice as control. GAPDH,
glyceraldehyde-3-phosphate dehydrogenase.
View larger version (44K):
[in a new window]
Fig. 6.
The high expression of sarcolipin mRNA in
the human atria. Abundant SLN expression was also detected in the
human atria but not in the ventricles. The expression was most abundant
in skeletal muscle. Using a mouse SERCA1 cDNA probe, no
hybrydization signal was detected in the human atria. GAPDH,
glyceraldehyde-3-phosphate dehydrogenase.
DISCUSSION
TOP
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
REFERENCES
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Dr. Tomoyuki Nakamura and Dr. Yoji Sato for stimulating discussion, Dr. Paul Grossfeld for critical reading of the manuscript, Ms. Barbara Levene for language editing of the manuscript, and Ms. Keiko Komatsu for preparation of paraffin sections.
![]() |
FOOTNOTES |
---|
* This work was supported in part by an open research grant from the Japan Research Promotion Society for Cardiovascular Diseases (2001).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ To whom correspondence may be addressed: Dept. of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Tel.: 81-33353-8111, ext. 24064; Fax: 81-33352-3088; E-mail: sminamis@ med.yokohama-cu.ac.jp or rumiko{at}lmcir.twmu.ac.jp.
Published, JBC Papers in Press, January 6, 2003, DOI 10.1074/jbc.M213132200
2 S. Miamisawa, Y. Wang, and K. R. Chen, unpublished observations.
![]() |
ABBREVIATIONS |
---|
The abbreviations used are: SLN, sarcolipin; SR, sarcoplasmic reticulum; SERCA, SR Ca2 ATPase; PLN, phospholamban; GFP, green fluorescent protein; TES, 2-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}ethanesulfonic acid; ANF, atrial natriuretic factor; BNP, brain natriuretic peptide.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1. | Wawrzynow, A., Theibert, J. L., Murphy, C., Jona, I., Martonosi, A., and Collins, J. H. (1992) Arch Biochem. Biophys. 298, 620-623[CrossRef][Medline] [Order article via Infotrieve] |
2. | Odermatt, A., Taschner, P. E., Scherer, S. W., Beatty, B., Khanna, V. K., Cornblath, D. R., Chaudhry, V., Yee, W. C., Schrank, B., Karpati, G., Breuning, M. H., Knoers, N., and MacLennan, D. H. (1997) Genomics 45, 541-553[CrossRef][Medline] [Order article via Infotrieve] |
3. |
Odermatt, A.,
Becker, S.,
Khanna, V. K.,
Kurzydlowski, K.,
Leisner, E.,
Pette, D.,
and MacLennan, D. H.
(1998)
J. Biol. Chem.
273,
12360-12369 |
4. |
Asahi, M.,
Kurzydlowski, K.,
Tada, M.,
and MacLennan, D. H.
(2002)
J. Biol. Chem.
277,
26725-26728 |
5. | Tada, M., and Toyofuku, T. (1996) J. Card. Fail. 2 Suppl. 4, S77-S85[Medline] [Order article via Infotrieve] |
6. | Luo, W., Grupp, I. L., Harrer, J., Ponniah, S., Grupp, G., Duffy, J. J., Doetschman, T., and Kranias, E. G. (1994) Circ. Res. 75, 401-409[Abstract] |
7. |
Koss, K. L.,
and Kranias, E. G.
(1996)
Circ. Res.
79,
1059-1063 |
8. | Minamisawa, S., Hoshijima, M., Chu, G., Ward, C. A., Frank, K., Gu, Y., Martone, M. E., Wang, Y., Ross, J., Jr., Kranias, E. G., Giles, W. R., and Chien, K. R. (1999) Cell 99, 313-322[Medline] [Order article via Infotrieve] |
9. |
Sato, Y.,
Kiriazis, H.,
Yatani, A.,
Schmidt, A. G.,
Hahn, H.,
Ferguson, D. G.,
Sako, H.,
Mitarai, S.,
Honda, R.,
Mesnard-Rouiller, L.,
Frank, K. F.,
Beyermann, B.,
Wu, G.,
Fujimori, K.,
Dorn, G. W., II,
and Kranias, E. G.
(2001)
J. Biol. Chem.
276,
9392-9399 |
10. |
Koss, K. L.,
Ponniah, S.,
Jones, W. K.,
Grupp, I. L.,
and Kranias, E. G.
(1995)
Circ. Res.
77,
342-353 |
11. |
Tupling, A. R.,
Asahi, M.,
MacLennan, D. H.,
Kurzydlowski, K.,
and Tada, M.
(2002)
J. Biol. Chem.
277,
44740-44746 |
12. |
Liao, P.,
Georgakopoulos, D.,
Kovacs, A.,
Zheng, M.,
Lerner, D.,
Pu, H.,
Saffitz, J.,
Chien, K.,
Xiao, R. P.,
Kass, D. A.,
and Wang, Y.
(2001)
Proc. Natl. Acad. Sci. U. S. A.
98,
12283-12288 |
13. |
Hunter, J. J.,
Tanaka, N.,
Rockman, H. A.,
Ross, J., Jr.,
and Chien, K. R.
(1995)
J. Biol. Chem.
270,
23173-23178 |
14. |
Minamisawa, S.,
Gu, Y.,
Ross, J., Jr.,
Chien, K. R.,
and Chen, J.
(1999)
J. Biol. Chem.
274,
10066-10070 |
15. | Machida, S., Matsuoka, R., Noda, S., Hiratsuka, E., Takagaki, Y., Oana, S., Furutani, Y., Nakajima, H., Takao, A., and Momma, K. (2000) Dev. Dyn. 217, 37-49[CrossRef][Medline] [Order article via Infotrieve] |
16. | Edes, I., and Kranias, E. G. (1990) Circ. Res. 67, 394-400[Abstract] |
17. | Nakanishi, T., and Jarmakani, J. M. (1984) Am. J. Physiol. 246, H61-H625 |
18. | Grover, A. K., and Khan, I. (1992) Cell Calcium 13, 9-17[CrossRef][Medline] [Order article via Infotrieve] |
19. |
Tada, M.,
Yabuki, M.,
and Toyofuku, T.
(1998)
Ann. N. Y. Acad. Sci.
853,
116-129 |
20. |
Gayan-Ramirez, G.,
Vanzeir, L.,
Wuytack, F.,
and Decramer, M.
(2000)
J. Physiol.
524,
387-397 |
21. | Ganim, J. R., Luo, W., Ponniah, S., Grupp, I., Kim, H. W., Ferguson, D. G., Kadambi, V., Neumann, J. C., Doetschman, T., and Kranias, E. G. (1992) Circ. Res. 71, 1021-1030[Abstract] |
22. |
Moorman, A. F.,
Vermeulen, J. L.,
Koban, M. U.,
Schwartz, K.,
Lamers, W. H.,
and Boheler, K. R.
(1995)
Circ. Res.
76,
616-625 |
23. |
Luo, W.,
Wolska, B. M.,
Grupp, I. L.,
Harrer, J. M.,
Haghighi, K.,
Ferguson, D. G.,
Slack, J. P.,
Grupp, G.,
Doetschman, T.,
Solaro, R. J.,
and Kranias, E. G.
(1996)
Circ. Res.
78,
839-847 |
24. |
Dash, R.,
Kadambi, V.,
Schmidt, A. G.,
Tepe, N. M.,
Biniakiewicz, D.,
Gerst, M. J.,
Canning, A. M.,
Abraham, W. T.,
Hoit, B. D.,
Liggett, S. B.,
Lorenz, J. N.,
Dorn, G. W., II,
and Kranias, E. G.
(2001)
Circulation
103,
889-896 |
25. | Mascioni, A., Karim, C., Barany, G., Thomas, D. D., and Veglia, G. (2002) Biochemistry 41, 475-482[CrossRef][Medline] [Order article via Infotrieve] |