Serpinins: Role in granule biogenesis, inhibition of cell death and cardiac function

Y. P. Loh, H. Koshimizu, N. X. Cawley, B. Tota

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Serpinins are a family of peptides derived from proteolytic cleavage of the penultimate and the last pair of basic residues at the C-terminus of Chromogranin A. Three forms of naturally occurring serpinin have been found in AtT-20 pituitary cells and rat heart. They are serpinin, pyrogutaminated (pGlu) -serpinin and a C-terminally extended form, serpinin-RRG. In addition pGlu-serpinin has been found in brain, primarily in neurites and nerve terminals and shown to have protective effects against oxidative stress on neurons and pituitary cells. Serpinin has also been demonstrated to regulate granule biogenesis in endocrine cells by up-regulating the protease inhibitor, protease nexin-1 transcription via a cAMP-PKA-sp1 pathway. This leads to inhibition of granule protein degradation in the Golgi complex which in turn promotes granule formation. More recently, pGlu-serpinin has been demonstrated to enhance both myocardial contractility (inotropy) and relaxation (lusitropy). In the Langendorff perfused rat heart, pGlu-serpinin showed a concentration-dependent positive inotropic effect exerted through a cAMP-PKA dependent pathway. In conclusion, the serpinin peptides have profound effects at many levels that affect the endocrine and nervous systems and cardiac function.

本文言語English
ページ(範囲)4086-4092
ページ数7
ジャーナルCurrent Medicinal Chemistry
19
24
DOI
出版ステータスPublished - 08-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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