Altered expression of nuclear and cytoplasmic histone H1 in pulmonary artery and pulmonary artery smooth muscle cells in patients with IPAH

Megha Talati, Erin Seeley, Kaori Ihida-Stansbury, Horace Delisser, Hayes McDonald, Fei Ye, Xueqiong Zhang, Yu Shyr, Richard Caprioli, Barbara Meyrick

研究成果: Article同行評審

5 引文 斯高帕斯(Scopus)

摘要

The pathogenesis of idiopathic pulmonary hypertension is poorly understood. This paper utilized histology-based Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS) to identify as-yet unknown proteins that may be associated with the structural changes in the pulmonary arterial walls of patients with IPAH. The technology identified significant increases in two fragments of histone H1 in the IPAH cases compared to controls. This finding was further examined using immunofluorescence techniques applied to sections from IPAH and control pulmonary arteries. In addition, cultured pulmonary artery smooth muscle cells (PASMCs) were utilized for Western analysis of histone H1 and importin β and importin 7, immunoprecipitation and assessment of nucleosomal repeat length (NRL). Immunofluorescence techniques revealed that nuclear expression of histone H1 was decreased and the chromatin was less compact in the IPAH cases than in the controls; furthermore, some cases showed a marked increase in cytoplasmic histone H1 expression. Using nuclear and cytoplasmic fractions of cultured PASMCs, we confirmed the reduction in histone H1 in the nucleus and an increase in the cytoplasm in IPAH cells compared to controls. Immunoprecipitation demonstrated a decreased association of histone H1 with importin β while importin 7 was unchanged in the IPAH cells compared to controls. The assessment of NRL revealed that the distance between nucleosomes was increased by ~20 bp in IPAH compared to controls. We conclude that at least two factors contribute to the reduction in nuclear histone H1—fragmentation of the protein and decreased import of histone H1 into the nucleus by importins. We further suggest that the decreased nuclear H1 contributes the less compact nucleosomal pattern in IPAH and this, in turn, contributes to the increase in NRL.

原文English
頁(從 - 到)340-351
頁數12
期刊Pulmonary Circulation
2
發行號3
DOIs
出版狀態Published - 2012 七月

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

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