Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats

Hidekazu Suzuki, Frank A. Delano, Neema Jamshidi, Dan Katz, Mikiji Mori, Kenjiro Kosaki, Roberta A. Gottlieb, Hiromasa Ishii, Geert W. Schmid-Schönbein

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)H2135-H2140
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number6 45-6
DOIs
Publication statusPublished - 1999 Jun

Keywords

  • Adrenalectomy
  • Apoptosis
  • Glucocorticoid
  • In situ deoxyribonucleic acid nick-end labeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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