|
|
|
|||||||
|
|||||||||
(Received for publication, August 8, 1995; and in revised form, October 30, 1995) From the
Ventricular cardiomyocytes have been identified as target cells
for parathyroid hormone (PTH). A structurally related peptide hormone,
parathyroid hormone-related peptide (PTH-rP), is expressed in the
heart. In the present study, it was investigated whether PTH-rP can
mimic or modify effects of PTH on cardiomyocytes. The investigated
effect was induction of creatine kinase (CK) activity, which is
associated with cardiac hypertrophy. PTH and PTH-rP have a similar
secondary structure within the active domain 28-34, with
exception of amino acid 29. At this position the hydrophilic glutamine
in the PTH molecule corresponds to hydrophobic alanine in the PTH-rP
molecule. Synthetic PTH or PTH-rP peptides covering domain 28-34
and recombinant full-length PTH(1-84) were used. PTH(28-48)
(100 nM) induced CK activity within 24 h (123 ± 3%;
means ± S.D., n = 4). PTH-rP(7-34) (1
nM to 1 µM) failed to induce CK activity in
cardiomyocytes. Given simultaneously, PTH-rP (1 µM)
reduced the stimulation of CK activity by PTH(1-84),
PTH(1-34), and PTH(28-48) by 94 ± 9, 79 ± 8,
and 69 ± 14%, respectively (means ± S.D., n = 4). In contrast, PTH-rP(7-34) was sufficient to
stimulate proliferation of chicken chondrocytes. Thus, PTH-rP exerts
different effects on cardiomyocytes and classical target cells for PTH. A synthetic hybrid peptide was synthesized,
[Ala
Cardiac myocytes have been identified as target cells for
parathyroid hormone (PTH)( Our study focused
on the midregional part of the PTH molecule, covering amino acids
28-34. This part of the molecule has been identified as the core
of a protein kinase C-activating domain of PTH and PTH-rP (7, 8, 9, 10, 11) . The
secondary structure of the two peptide hormones in this region is very
similar(12) , consisting of a helical motif. In PTH, the
hydrophobic amino acids are placed on one side and the hydrophilic
amino acids on the other side (Fig. 1). In PTH-rP, the exception
to this rule is that the hydrophobic alanine is located at position 29, i.e. in a hydrophilic environment. The role of this amino acid
in the structure-function relationship of the two peptide hormones was
analyzed specifically in this study. For this purpose two mutated
proteins were synthesized: mutant
[Ala
Figure 1:
Helix wheels of the 28-48 region
of PTH, PTH-rP, and the PTH mutants
[Asn
Isolated
cardiomyocytes from the ventricular myocardium of the adult rat were
used as an experimental model. In this preparation other cells are
absent and the cardiomyocytes are mechanically quiescent. The parameter
under investigation was the induction of cytosolic CK, a characteristic
feature of the hypertrophic response of cardiomyocytes to PTH
stimulation(3) . To compare the effects of PTH-rP on
cardiomyocytes with those of classical target cells, we also used
primary cultures of chicken derived chondrocytes. This cell system has
been used previously to identify the protein-kinase C-dependent domain
of PTH(9) . PTH stimulates the proliferation of chicken
chondrocytes, and incorporation of [
Four hours after
plating, cultures were washed twice with culture medium to remove round
and non-attached cells. The remaining cultures consisted of >95%
rod-shaped cells. Following this washing procedure, experimental media
were added in which the cells were incubated at 37 °C for the times
indicated. The experimental media consisted of the basic culture medium
(control) and the following additions, as indicated: PTH peptides
(human PTH(1-84), bovine PTH(1-34), human PTH(28-48),
human [Asn Chondrocytes were isolated from sterna of 16-day-old embryonic
chicks as described previously(9) . Chondrocytes were seeded
into microtiter plates with 96 wells (6-mm diameter; 14,000
cells/cm
The distribution of the
cytosolic isoenzymes of creatine kinase, MM, MB, and BB, was analyzed
as described previously(3) . The supernatants were applied to
1-ml DEAE-cellulose columns that had been equilibrated with SAE-buffer
(composition in mM: 20 NaCl, 5 magnesium acetate, 0.4 EDTA,
and 100 Tris/HCl; pH 7.9). The CK-MM isoenzyme eluted directly with
this buffer, the CK-MB isoenzyme with change of NaCl concentration to
40 mM and pH to 6.4, the CK-BB with change of NaCl
concentration to 250 mM and pH 6.4.
Figure 2:
Stimulation of cytosolic CK activity by
24-h exposure of cardiomyocytes to various concentrations of
PTH(1-84) or PTH(1-34). Data are given as mean values
± S.D. of four cultures; different from control: *, p < 0.05. Basal activity of CK was 3.2 ± 0.5 units/mg
protein.
Figure 3:
Schematic drawing of the PTH and PTH-rP
variants used in the experiments. Black indicates parts with
high homology on the basis of amino acid composition, gray indicates parts with structural homology, and white indicates parts without homology. AC and PKC indicate the position of adenylate cyclase-activating domain and
protein kinase C-activating domain of the peptides. The numbers indicate the number of amino acids.
Figure 4:
Stimulation of cytosolic CK activity by
24-h exposure of cardiomyocytes to various concentrations of
PTH(28-48) or PTH-rP(7-34). Data are given as mean values
± S.D. of four cultures; different from control: *, p < 0.05. Basal activity of CK was 3.7 ± 0.2 units/mg
protein.
Figure 5:
Inhibition of cytosolic CK activity by
24-h exposure of cardiomyocytes to 100 nM PTH(28-48) and
simultaneously PTH-rP(7-34) in various concentrations. Data are
given as mean values ± S.D. of four cultures; different from
control: *, p < 0.05. The 100% value of stimulated
cardiomyocytes incubated with PTH(28-48) but without
PTH-rP(7-34) was 4.6 ± 0.3 units/mg protein, and basal
activity of untreated controls was 3.4 ± 0.2 units/mg
protein.
Figure 6:
Inhibition of cytosolic CK activity by
24-h exposure of cardiomyocytes to PTH(1-34) (100 nM)
and simultaneously PTH-rP(1-34) in various concentrations. Data
are given as mean values ± S.D. of four cultures; different from
control: *, p < 0.05. The 100% value of stimulated
cardiomyocytes incubated with PTH(1-34) but without PTH-rP was
4.3 ± 0.7 units/mg protein, and basal activity of untreated
controls was 3.2 ± 0.3 units/mg
protein.
The question was investigated
whether the three cytosolic isoenzymes of creatine kinase, i.e. CK-MM, CK-MB, and CK-BB, were differently induced in cells treated
with PTH(28-48). PTH(28-48) (300 nM) increased
only the activity of CK dimers containing the B-isoform: The CK-MB
activity was increased to 175%, and the CK-BB activity to 118%. CK-MM
activity was not significantly enhanced (Fig. 7). Simultaneous
addition of PTH-rP(7-34) (1 µM) abolished the
induction of CK-MB and CK-BB through 100 nM PTH(28-48).
Figure 7:
Distribution of isoenzymes of cytosolic CK
in cardiomyocytes. Specific activities of isoenzymes (CK-MM, CK-MB,
CK-BB) after 24-h incubations in presence of PTH(28-48) (PTH, 100 nM) or PTH(28-48) with
PTH-rP(7-34) (PTH+PTH-rP, 100 nM, 1
µM). Mean values of isoenzyme activities under control
conditions were set at 100%; these were 2.88 ± 0.09 units/mg
protein for CK-MM, 0.17 ± 0.01 units/mg protein for CK-MB, and
0.49 ± 0.14 units/mg protein for CK-BB. Data are means +
S.D.; n = 4. Differences from control: *, p < 0.05.
Figure 8:
Thymidine incorporation by 24-h exposure
of chicken chondrocytes to various concentrations of PTH-rP(1-34)
and PTH-rP(7-34). Data are given as mean values ± S.D. of
four cultures; different from control: *, p < 0.05. The
basal thymidine incorporation of control chondrocytes was 229 ±
31 cpm.
Figure 9:
Stimulation of CK activity by
[Ans
Figure 10:
Inhibition of cytosolic CK activity in
24-h cultures of cardiomyocytes cultivated in presence of
PTH(28-48) (100 nM) and simultaneously
[Asn
Figure 11:
Inhibition of cytosolic CK activity by
24-h exposure of cardiomyocytes to phorbol myristate acetate (PMA) (100 nM) and simultaneously
[Ala
It was further investigated whether PTH-rP
peptides and the mutated antagonistic PTH peptide are able to
antagonize CK induction of naturally occurring full-length
PTH(1-84) on cardiomyocytes as well. Induction of CK-activity by
PTH(1-84) was antagonized by either PTH-rP(1-34) or
[Ala
Figure 12:
Inhibition of cytosolic CK activity by
24-h exposure of cardiomyocytes to PTH(1-84) (10 nM) and
simultaneously PTH-rP(1-34) or
[Ala
In the present study the question was investigated whether
PTH-rP, a peptide expressed in myocardial tissue, can mimic or modulate
the ability of PTH to induce cytosolic CK in ventricular
cardiomyocytes. The main finding of the present study is that PTH and
PTH-rP have comparable effects on classical target cells, i.e. chondrocytes, but PTH-rP cannot mimic the action of PTH in
cardiomyocytes. PTH stimulated cytosolic CK activity of cardiomyocytes
by inducing the fetal type B-isoform. In contrast, PTH-rP had no such
effect. The present study has revealed for the first time that
PTH-rP may act indirectly on cardiomyocytes, even if lacking a direct
effect. PTH-rP(1-34) and PTH-rP(7-34) were found to
antagonize the ability of PTH(28-48) and full-length
PTH(1-84) to induce cytosolic CK. When at position 29 a
hydrophobic residue (alanine) was introduced into the PTH(28-48)
molecule, a mutant peptide was obtained that was functionally
equivalent to PTH-rP(7-34). It antagonized the effect of
full-length PTH(1-84) and PTH(28-48) but lacked intrinsic
activity. In case of a hydrophilic replacement at position 29, the
activity of PTH(28-48) was not altered. The results show that
position 29 is essential for the function of the core domain of PTH,
possibly due to the formation of a hydrogen bond. The results also
suggest that PTH-rP competes with PTH for the same binding site but
lacks intrinsic activity due to this structural differences within the
core of the functional domain. The antagonism between
PTH(28-48) and peptides with hydrophobic replacement at position
29 are not due to adverse effects at the intracellular key step (3) for the induction of CK, i.e. protein kinase C. In
experiments where protein kinase C was stimulated directly by a phorbol
ester, [Ala It has been reported that PTH and PTH-rP differ also in other
effects on adult cardiomyocytes; PTH but not PTH-rP was found to
increase intracellular calcium(19) . In the murine osteoblastic
cell line MCT3T3-E1 (20) and in human placenta(21) ,
PTH-rP was also found unable to mimic the action of PTH. These studies
did not investigate, however, whether PTH-rP antagonized the effects of
PTH on the investigated cell types and did not identify the structural
cause for a difference in the action between the two peptide hormones. In conclusion, the results of this study demonstrate a marked
difference for the effects of PTH and PTH-rP on cardiomyocytes but not
on chondrocytes. The results offer the opportunity to design
heart-specific antagonists of PTH similar to
[Ala
Volume 271,
Number 6,
Issue of February 9, 1996 pp. 3074-3078
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS
DISCUSSION
FOOTNOTES
ACKNOWLEDGEMENTS
REFERENCES
]PTH(28-48), in which alanine replaced
glutamine at position 29, as in the PTH-rP molecule. In contrast to
PTH(28-48), this mutated peptide
[Ala
]PTH(28-48) had no intrinsic activity
but antagonized the effect of PTH(1-84) and PTH(28-48) on
cardiomyocytes. The results demonstrate that on cardiomyocytes the
effect of PTH can be antagonized by PTH-rP. This antagonism seems due
to a hydrophobic replacement at position 29.
)(1, 2) . We
found recently that PTH exerts a hypertrophic effect on adult
cardiomyocytes, characterized by an increase in protein synthesis and a
selective induction of cytosolic creatine kinase (CK)(3) .
Parathyroid hormone-related peptide (PTH-rP) is a peptide hormone
structurally related to PTH. Both peptide hormones have a strong
homology in the N-terminal part of the molecule and can bind to the
same receptor(4) . In contrast to PTH, which is synthesized in
the parathyroidea, PTH-rP is expressed in many tissues including the
heart(5, 6) . Direct effects of PTH-rP on myocardial
cells have not been investigated before. The aim of the present study
was to compare the effects of PTH-rP and PTH on cardiomyocytes with
their effects on classical target cells for PTH, i.e. chondrocytes. Recombinant full-length PTH and commercially
available synthetic peptides, either covering the protein kinase
C-activating domain and the N-terminally located adenylate cyclase
activating domain of PTH, or N-truncated peptides, covering exclusively
the protein kinase C-activating domain, were used.]PTH(28-48), in which the hydrophilic
glutamine at position 29 of the PTH molecule is replaced by the
hydrophobic alanine, as in the PTH-rP molecule; and
[Ans
]PTH(28-48), in which glutamine is
replaced conservatively by the hydrophilic asparagine.
]PTH(28-48) (N29Q) and
[Ala
]PTH(28-48) (A29Q). Hydrophobic amino
acids are hatched. In the PTH mutant
[Asn
]PTH(28-48), a hydrophilic amino acid
is replaced by another hydrophilic amino acid. In the mutant
[Ala
]PTH(28-48) at position 29, glutamine
is replaced by alanine which is at position 29 in
PTH-rP.
H]thymidine
was determined as a measure of DNA synthesis.
Cell Culture
Ventricular heart muscle cells were
isolated from 200-250-g male Wistar rats as described
previously(13) . Isolated cells were suspended in serum-free
culture medium and plated at a density of 4 
10
cells/60-mm culture dish (Falcon 3004). The culture dishes had
been preincubated overnight with 4% fetal calf serum in medium 199. The
basic culture medium consisted of modified glutamine-free medium 199
with Earle's salts, 5 mM creatine, 2 mML-carnitine, 5 mM taurine, 100 IU/ml penicillin,
and 100 µg/ml streptomycin(14) . To prevent growth of
nonmyocytes, media were also supplemented with 10 µM cytosine 
-D-arabinofuranoside.]PTH(28-48), human
[Ala
]PTH(28-48)) and PTH-rP peptides
(human PTH-rP(1-34) and human PTH-rP(7-34)). Ascorbic acid
(100 µM) was added to the culture media as an antioxidant.
) and a 200-µl volume of medium 199 containing
10% fetal calf serum. After 17 h, the medium was replaced by 200 µl
of serum-free medium 199. After 4 days the cultures were used for
determination of DNA synthesis.Analysis of Creatine Kinase Activity
Specific
activities of the cytosolic enzyme creatine kinase were determined as
follows: Cultures were first washed twice with phosphate-buffered
saline (composition in mM: 137 NaCl, 2.6 KCl, 1.5
KHPO
, and 8.1 NaHPO; pH
7.4). After addition of creatine kinase assay-buffer (composition in
mM: 5 magnesium acetate, 0.4 EDTA, 2.5 dithioerythritol, 50
Tris/HCl, and 250 sucrose; pH 6.8) to the dishes, the cells were
scraped off, homogenized, and frozen until use at -14 °C. For
analysis these samples were thawed, and the resulting suspension was
sonicated and centrifuged at 12,000 g for 2 min. The
supernatants were used for enzyme analysis. The activity of creatine
kinase was determined according to Gerhardt (15) using
standard ultraviolet methods. Protein contents were determined
according to Bradford(16) .Assay for Thymidine Incorporation in
Chondrocytes
The rate of DNA-synthesis was assayed in monolayer
cultures of chondrocytes by the incorporation of
[H]thymidine into perchloric acid-precipitable
material as described previously(9) . Briefly, chondrocyte
cultures were incubated for 4 h with the appropriate effector and 1
µCi of [H]thymidine. Subsequently, medium was
removed and the cells were washed twice with 200 µl of
phosphate-buffered saline. Then cells were lysed by 100 µl of 2%
(v/v) Nonidet P-40 and 2% (w/v) sodium dodecyl sulfate treatment and
perchloric-insoluble material was precipitated by adding an equal
volume of 2% (w/v) perchloric acid in presence of 1% herring sperm DNA
as carrier. After storage for 10 min at -20 °C, the
precipitated material of each well was transferred to glass fiber
filters with a Scatron-As semiautomatic cell harvester. Filters were
dried at 80 °C for 20 min, transferred to scintillation vials, and
2 ml of scintillation mixture were added. Radioactivity of the samples
was determined with a -counter.Peptide Synthesis and Purification
The PTH mutants
[Asn]PTH(28-48) and
[Ala
]PTH(28-48) were assembled with a
Milligen 9050 automatic peptide synthesizer on
Fmoc-Ser(t-butyl)NovaSyn PA 500 resins. Fmoc amino acids were
used in a 3-fold excess and activated with
2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluroniumtetrafluoroborate
and diisopropylethylamine in equal molar ratios. Aspartic acid was t-butyl-protected, asparagine and histidine with trityl,
arginine with pentamethyl-chroman. After completion of the synthesis,
the dried resins were treated for 3 h with trifluoroacetic acid
containing 3% triisobutylsilane and 2% water (10 ml/g resin). The
resins were removed by filtration and washed several times with acetic
acid, and the combined filtrate and washings were evaporated to near
dryness. The peptides were precipitated by the addition of t-butyl methylether and collected by centrifugation. After two
resuspensions in ether and centrifugations, the precipitates were dried
in a vacuum. The crude peptides were dissolved in water/acetonitrile
1:1 and passed over 6-ml octadecyl disposable extraction columns. After
rinsing the columns with acetonitrile, most of the acetonitrile of the
combined eluents was evaporated. The samples were lyophilized and the
resulting crude peptides analyzed by high performance liquid
chromatography. Purification was carried out by preparative
reverse-phase high performance liquid chromatography (C-18) with
water/acetonitrile gradients containing 0.5% trifluoroacetic acid. The
purified peptides were lyophilized and characterized by amino acid
analysis and fast atom bombardment mass spectrometry.
Materials
Falcon tissue culture dishes were
purchased from Becton-Dickinson (Heidelberg, Germany). Boehringer
Mannheim (Mannheim, Germany) was the source for the medium 199 and
fetal calf serum. PTH(1-34), PTH(28-48),
PTH-rP(1-34), and PTH-rP(7-34) were obtained from Sigma
(Deisenhofen, Germany). Recombinant full-length PTH(1-84) was
synthesized according to (17) . All other chemicals were of
analytical grade.Statistics
Data are given as means ± S.D.
from n different culture preparations. Statistical comparisons
were performed by one-way analysis of variance and use of the
Bonferroni test for post hoc analysis(18) .
Differences with p < 0.05 were regarded as significant.
Effects of PTH and PTH-rP on Creatine Kinase Activity
of Cardiomyocytes
The specific activity of cytosolic CK was
determined in 24-h-old cultures in presence of full-length PTH
(PTH(1-84)) or PTH(1-34)). In classical target cells for
PTH, the latter is a full biological agonist. Both PTH variants
increased CK activity of cardiomyocytes dose-dependently. Full-length
PTH exerted its maximal effect at a 10-fold lower concentration than
PTH(1-34); the maximal effects were identical (Fig. 2).
PTH(1-84) and PTH(1-34) cover two distinct functional
domains: the N-terminal located adenylate cyclase activating domain and
the protein kinase C-activating domain located in the 28-34
region. For clarity, a schematic figure of the PTH and PTH-rP variants
used in these experiments is given in Fig. 3. To avoid possible
side effects of the N-terminally located adenylate cyclase activating
domain of PTH or PTH-rP, N-truncated PTH or PTH-rP peptides, i.e. PTH(28-48) or PTH-rP(7-34), were also used. Compared
to control conditions, PTH(28-48) (1 µM) increased
the activity of CK to 141% (Fig. 4). In contrast,
PTH-rP(7-34) (1 nM to 1 µM) had no effect.
When PTH-rP(7-34) was added simultaneously with PTH(28-48)
(100 nM) to the cultures, PTH-rP(7-34) decreased
dose-dependently the stimulation of CK by PTH(28-48), with a
two-thirds reduction at 100 nM PTH-rP(7-34) (Fig. 5). PTH(28-48) and PTH-rP(7-34) differ in the
length of adjacent C-terminal amino acids. To exclude effects of these
C-terminally located amino acids PTH(1-34) and PTH-rP(1-34)
were also tested. As shown in Fig. 6, 1 µM PTH-rP(1-34) antagonized the induction of CK through 100
nM PTH(1-34) too.
Effect of PTH-rP on DNA Synthesis of
Chondrocytes
In contrast to the inability of PTH-rP peptides to
induce CK activity in cardiomyocytes, PTH-rP peptides significantly
induced DNA synthesis in chondrocytes. PTH-rP(1-34) and
PTH-rP(7-34) stimulated DNA synthesis to a similar extent, by 88%
and 82%, respectively (Fig. 8).
Effects of Mutated PTH Peptides on
Cardiomyocytes
The ability of PTH(28-48) to induce CK
activity was compared to the ability of mutated peptides. The
conservative mutant, [Asn]PTH(28-48),
stimulated CK activity of cardiomyocytes in a dose-dependent manner
(118 ± 4% at 100 nM). In contrast, the non-conservative
mutant, [Ala
]PTH(28-48), did not induce CK (Fig. 9). It was investigated by addition of PTH(28-48)
simultaneously with either [Ala
]PTH(28-48)
or [Asn
]PTH(28-48), whether these mutants
were able to antagonize the effect of PTH(28-48) on CK activity.
[Ala
]PTH(28-48), which lacked intrinsic
activity, antagonized the effect of PTH(28-48) in a
dose-dependent manner. At 1 µM, a three-fourths inhibition
was observed (Fig. 10).
[Asn
]PTH(28-48) did not inhibit
CK-induction by PTH(28-48). When a phorbol ester, which directly
activates protein kinase C, was used to induce CK activity through a
receptor-independent route, the mutant
[Ala
]PTH(28-48) had no antagonistic effect (Fig. 11).
]PTH(28-48) and
[Ala
]PTH(28-48) at various concentrations.
Data are given as mean values ± S.D. of four cultures; different
from control: *, p < 0.05. Basal activity of CK was 3.7
± 0.2 units/mg protein.
]PTH(28-48) or
[Ala
]PTH(28-48) at the indicated
concentrations. Data are means ± S.D. of four cultures;
different from control: *, p < 0.05. The 100% value of
cardiomyocytes cultivated for 24 h in presence of PTH(28-48) (100
nM) was 4.7 ± 0.3 units/mg protein, and basal activity
of untreated controls was 3.6 ± 0.4 units/mg
protein.
]PTH(28-48) in various concentrations.
Data are means + S.D. of four cultures; different from control: *, p < 0.05. The 100% value of stimulated cardiomyocytes
incubated with phorbol myristate acetate (100 nM) but without
[Ala
]PTH(28-48) was 5.1 ± 0.4
units/mg protein, and basal activity for untreated controls was 3.5
± 0.4 units/mg protein.
]PTH(28-48) to 94 ± 8 and 82
± 5%, respectively (Fig. 12).
]PTH(28-48) in various concentrations.
Data are means ± S.D. of four cultures; different from control:
*, p < 0.05. The 100% value of stimulated cardiomyocytes
incubated with PMA but without PTH-rP(1-34) or
[Ala
]PTH(28-48) was 5.7 ± 0.5
units/mg protein and for untreated controls 3.8 ± 0.4 units/mg
protein.
]PTH(28-48) had no antagonistic
effect. This finding supports the hypothesis that the antagonism
between the peptides is due to a competition at sarcolemmal binding
sites.
]PTH(28-48) used in this study. Our
results further indicate that PTH peptides, covering the 28-34
region of PTH, are full biological agonists in respect to CK induction
on cardiomyocytes. In contrast, PTH-rP, which is expressed in
myocardial tissue itself, seems to function as a paracrine modulator of
the hypertrophic effects of PTH in cardiac muscle.
)
We acknowledge the technical assistance of D.
Schreiber and H. Holzträger.
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Tastan, R. Schreckenberg, S. Mufti, Y. Abdallah, H. M. Piper, and K.-D. Schluter Parathyroid hormone improves contractile performance of adult rat ventricular cardiomyocytes at low concentrations in a non-acute way Cardiovasc Res, April 1, 2009; 82(1): 77 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Meyer, R. Schreckenberg, F. Kretschmer, A. Bittig, C. Conzelmann, C. Grohe, and K.-D. Schluter Parathyroid hormone-related protein (PTHrP) signal cascade modulates myocardial dysfunction in the pressure overloaded heart Eur J Heart Fail, December 1, 2007; 9(12): 1156 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-D. Schluter, C. Katzer, K. Frischkopf, S. Wenzel, G. Taimor, and H. M. Piper Expression, Release, and Biological Activity of Parathyroid Hormone-Related Peptide From Coronary Endothelial Cells Circ. Res., May 12, 2000; 86(9): 946 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-D. Schluter PTH and PTHrP: Similar Structures but Different Functions Physiology, December 1, 1999; 14(6): 243 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-D. Schluter and H. M. Piper Cardiovascular actions of parathyroid hormone and parathyroid hormone-related peptide Cardiovasc Res, January 1, 1998; 37(1): 34 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sawada, M. Suda, H. Yokoyama, T. Kanda, T. Sakamaki, S. Tanaka, R. Nagai, S. Abe, and T. Takeuchi Stretch-induced Hypertrophic Growth of Cardiocytes and Processing of Brain-type Natriuretic Peptide Are Controlled by Proprotein-processing Endoprotease Furin J. Biol. Chem., August 15, 1997; 272(33): 20545 - 20554. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |