Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats.
The mechanisms contributing to organ injury in hypertension have been incompletely defined. The thymus gland of the spontaneously hypertensive rat (SHR) shows significant atrophy at the age of 15 wk compared with its normotensive control, the Wistar-Kyoto rat (WKY). The aim of the present study was to examine the thymus of SHR for evidence of DNA nicking as one of the mechanisms for thymic atrophy. SHR and WKY were subjected to adrenalectomy or sham surgery at 12 wk and studied at 15 wk. Adrenalectomy served to normalize the blood pressure in the SHR. DNA nicking was detected by in situ nick-end labeling (ISEL) of fixed tissue sections. Tissue sections were treated with proteolysis, and terminal deoxyribonucleotidyl transferase was used to incorporate biotinylated deoxynucleotides into DNA nick end in situ. Separately, DNA fragmentation was evaluated by measuring the level of released mono- and oligonucleosomes to the cytoplasm. A higher number of thymic ISEL-positive cells and a higher level of cytoplasmic mono- and oligonucleosomes were observed in SHR than in WKY. After adrenalectomy the enhanced level of ISEL and cytoplasmic mono- and oligonucleosomes in SHR was reduced to the level in WKY. Dexamethasone treatment (0.05 mg. kg-1. day-1) in WKY serves to decrease the thymus weight and significantly elevate the level of mono- and oligonucleosomes. Thus increased DNA fragmentation represents one of the mechanisms associated with thymic atrophy, a feature that reflects immune suppression in SHR.
Suzuki
H
H
Department of Bioengineering and Institute for Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093-0412, USA. hsuzuki@mc.med.keio.ac.jp
Delano
F A
FA
Jamshidi
N
N
Katz
D
D
Mori
M
M
Kosaki
K
K
Gottlieb
R A
RA
Ishii
H
H
Schmid-Schönbein
G W
GW
D000315:Adrenalectomy; D000818:Animals; D001284:Atrophy; D001794:Blood Pressure / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005821:Genetic Techniques; D005938:Glucocorticoids / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D009707:Nucleosomes / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011921:Rats, Inbred WKY; D012016:Reference Values; D013950:Thymus Gland / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D005938:Glucocorticoids; D009707:Nucleosomes; D003907:Dexamethasone