Role of pGlu-serpinin, a novel chromogranin a-derived peptide in inhibition of cell death

Hisatsugu Koshimizu, Niamh X. Cawley, Alfred L. Yergy, Y. Peng Loh

研究成果: Article

14 引用 (Scopus)

抄録

Chromogranin A (CgA) is a member of the granin family of molecules found in secretory granules of endocrine and neuro-endocrine cells. Here, we have identified a new 23-mer CgA-derived peptide secreted from pituitary AtT-20 cells, which we named pyroGlu-serpinin (pGlu-serpinin). LC-MS studies of peptides in conditioned medium of AtT-20 cells indicate that pGlu-serpinin is derived from initial processing of mouse CgA at paired basic residues, Arg461-Arg462 and Arg433-Arg434, to yield a previously described 26 amino acid peptide, serpinin. Three amino acids are then cleaved from the N terminus of serpinin, yielding a peptide with an N-terminal glutamine, which is then subsequently pyroglutaminated. Immunocytochemistry showed co-localization of pGlu-serpinin with adrenocorticotropic hormone in secretory granules of AtT-20 cells, and it was released in an activity-dependent manner. Functional studies demonstrated that pGlu-serpinin was able to prevent radical oxygen species (hydrogen peroxide)-induced cell death of AtT-20 cells and cultured rat cerebral cortical neurons at a concentration of 1 and 10 nM, respectively. These data indicate that pGlu-serpinin has anti-apoptotic effects that may be important in neuroprotection of central nervous system neurons and pituitary cells. Furthermore, pGlu-serpinin added to the media of AtT-20 cells up-regulated the transcription of the serine protease inhibitor, protease nexin-1 (PN-1) mRNA. pGlu-serpinin's ability to increase levels of PN-1, a potent inhibitor of plasmin released during inflammatory processes causing cell death, may play a role in protecting cells under adverse pathophysiological conditions.

元の言語English
ページ(範囲)294-303
ページ数10
ジャーナルJournal of Molecular Neuroscience
45
発行部数2
DOI
出版物ステータスPublished - 01-10-2011

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Chromogranins
Cell Death
Peptides
Protease Nexins
Chromogranin A
Secretory Vesicles
Neurons
Amino Acids
Antifibrinolytic Agents
Serine Proteinase Inhibitors
Aptitude
Endocrine Cells
Conditioned Culture Medium
Glutamine
Adrenocorticotropic Hormone
Hydrogen Peroxide
Inhibition (Psychology)
Cultured Cells
Reactive Oxygen Species
Central Nervous System

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

これを引用

Koshimizu, Hisatsugu ; Cawley, Niamh X. ; Yergy, Alfred L. ; Loh, Y. Peng. / Role of pGlu-serpinin, a novel chromogranin a-derived peptide in inhibition of cell death. :: Journal of Molecular Neuroscience. 2011 ; 巻 45, 番号 2. pp. 294-303.
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Role of pGlu-serpinin, a novel chromogranin a-derived peptide in inhibition of cell death. / Koshimizu, Hisatsugu; Cawley, Niamh X.; Yergy, Alfred L.; Loh, Y. Peng.

:: Journal of Molecular Neuroscience, 巻 45, 番号 2, 01.10.2011, p. 294-303.

研究成果: Article

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AB - Chromogranin A (CgA) is a member of the granin family of molecules found in secretory granules of endocrine and neuro-endocrine cells. Here, we have identified a new 23-mer CgA-derived peptide secreted from pituitary AtT-20 cells, which we named pyroGlu-serpinin (pGlu-serpinin). LC-MS studies of peptides in conditioned medium of AtT-20 cells indicate that pGlu-serpinin is derived from initial processing of mouse CgA at paired basic residues, Arg461-Arg462 and Arg433-Arg434, to yield a previously described 26 amino acid peptide, serpinin. Three amino acids are then cleaved from the N terminus of serpinin, yielding a peptide with an N-terminal glutamine, which is then subsequently pyroglutaminated. Immunocytochemistry showed co-localization of pGlu-serpinin with adrenocorticotropic hormone in secretory granules of AtT-20 cells, and it was released in an activity-dependent manner. Functional studies demonstrated that pGlu-serpinin was able to prevent radical oxygen species (hydrogen peroxide)-induced cell death of AtT-20 cells and cultured rat cerebral cortical neurons at a concentration of 1 and 10 nM, respectively. These data indicate that pGlu-serpinin has anti-apoptotic effects that may be important in neuroprotection of central nervous system neurons and pituitary cells. Furthermore, pGlu-serpinin added to the media of AtT-20 cells up-regulated the transcription of the serine protease inhibitor, protease nexin-1 (PN-1) mRNA. pGlu-serpinin's ability to increase levels of PN-1, a potent inhibitor of plasmin released during inflammatory processes causing cell death, may play a role in protecting cells under adverse pathophysiological conditions.

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