title: Serpinins: role in granule biogenesis, inhibition of cell death and cardiac function.
abstract: 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.
authors: Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bldg. 49, Room 5A22, Bethesda, MD 20892, USA. lohp@mail.nih.gov
authors: Y P
authors: YP
authors: Loh
authors: H
authors: H
authors: Koshimizu
authors: N X
authors: NX
authors: Cawley
authors: B
authors: B
authors: Tota
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D053379:Chromogranin A / Q000737:chemistry / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053379:Chromogranin A; D058258:Serpin E2; C541127:Serpine2 protein, rat; D015843:Serpins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases