Relative sensitivity of kidney and bone to the amino-terminal fragment b-PTH (1–30) of native bovine parathyroid hormone: Implications for assessment of bioactivity of parathyroid hormone fragments in vivo and in vitro

1983 ◽  
Vol 35 (1) ◽  
pp. 520-525 ◽  
Author(s):  
Kevin J. Martin ◽  
Ezequiel Bellorin-Font ◽  
Jeremiah J. Morrissey ◽  
R. L. Jilka ◽  
Ronal R. MacGregor ◽  
...  
1978 ◽  
Vol 62 (2) ◽  
pp. 256-261 ◽  
Author(s):  
Kevin J. Martin ◽  
Jeffrey J. Freitag ◽  
Mary B. Conrades ◽  
Keith A. Hruska ◽  
Saulo Klahr ◽  
...  

Biochemistry ◽  
1972 ◽  
Vol 11 (10) ◽  
pp. 1973-1979 ◽  
Author(s):  
Henry T. Keutmann ◽  
Bess F. Dawson ◽  
Gerald D. Aurbach ◽  
John T. Potts

2004 ◽  
Vol 15 (6) ◽  
pp. 2804-2818 ◽  
Author(s):  
Gabriela Paroni ◽  
Michela Mizzau ◽  
Clare Henderson ◽  
Giannino Del Sal ◽  
Claudio Schneider ◽  
...  

Histone deacetylases (HDACs) are important regulators of gene expression as part of transcriptional corepressor complexes. Here, we demonstrate that caspases can repress the activity of the myocyte enhancer factor (MEF)2C transcription factor by regulating HDAC4 processing. Cleavage of HDAC4 occurs at Asp 289 and disjoins the carboxy-terminal fragment, localized into the cytoplasm, from the amino-terminal fragment, which accumulates into the nucleus. In the nucleus, the caspase-generated fragment of HDAC4 is able to trigger cytochrome c release from mitochondria and cell death in a caspase-9–dependent manner. The caspase-cleaved amino-terminal fragment of HDAC4 acts as a strong repressor of the transcription factor MEF2C, independently from the HDAC domain. Removal of amino acids 166–289 from the caspase-cleaved fragment of HDAC4 abrogates its ability to repress MEF2 transcription and to induce cell death. Caspase-2 and caspase-3 cleave HDAC4 in vitro and caspase-3 is critical for HDAC4 cleavage in vivo during UV-induced apoptosis. After UV irradiation, GFP-HDAC4 translocates into the nucleus coincidentally/immediately before the retraction response, but clearly before nuclear fragmentation. Together, our data indicate that caspases could specifically modulate gene repression and apoptosis through the proteolyic processing of HDAC4.


1975 ◽  
Vol 66 (3) ◽  
pp. 307-318 ◽  
Author(s):  
P. M. BARLING ◽  
G. N. HENDY ◽  
M. C. EVANS ◽  
J. L. H. O'RIORDAN

SUMMARY Immunoassays specific for limited regions of bovine parathyroid hormone were developed in four ways. With the heterogeneous antisera produced by immunizing with intact bovine parathyroid hormone (BPTH 1–84), the specificity of radioimmunoassays could be enhanced by presaturating either with an amino-terminal (BPTH 1–34) or carboxy-terminal (BPTH 53–84) fragment. Then, the antibodies which had not been neutralized reacted exclusively with the opposite end of the molecule, even using [125I]BPTH 1–84 as tracer. With some antisera, the appropriate fragment and intact hormone reacted identically. However, with other antisera, the fragment reacted less well than the intact hormone, possibly because these antisera contain antibodies reacting with the middle of the molecule. Using the labelled fragment ([125I]BPTH 1–34) as tracer, with heterogeneous antisera, radioimmunoassays specific for the amino-terminal region were obtained. With one antiserum, BPTH 1–34 reacted identically with the intact hormone, but with another antiserum, the fragment was more reactive than the intact molecule. A region-specific radioimmunoassay was also developed using antibodies produced by immunization with a fragment of the hormone. An antiserum raised against BPTH 1–34 had high affinity for the amino-terminal fragment, but reacted less well with the intact hormone. Immunoradiometric assays, specific for the amino- or carboxy-terminal regions, were developed by using immunoadsorbents consisting of a fragment (either BPTH 1–34 or BPTH 53–84) coupled to cellulose. These were used to fractionate 125I-labelled antibodies. With some of these selected antibodies, the appropriate fragment was of lower reactivity than the intact hormone. This may have been due to the presence of an incomplete antigenic site on the fragment, or to conformational differences between the fragment and the corresponding region of the intact hormone. With other selected antibodies the fragment and the intact molecule reacted identically. Careful selection of antisera and of technique is necessary to obtain an assay in which a fragment and the intact hormone behave identically.


Nephron ◽  
1991 ◽  
Vol 57 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Mohamed A. El-Shahawy ◽  
George Z. Fadda ◽  
James R. Wisner, Jr ◽  
Ian G. Renner ◽  
Hidecki Omachi ◽  
...  

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