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subsequently replenished. Our studies found that secreted serpinin and pGlu-ser-
pinin act as a signal to drive granule biogenesis likely through binding to a
G-protein coupled receptor (see chapter “Full Length CgA: A Multifaceted
Protein in Cardiovascular Health and Disease” by B. Tota) and triggering a cAMP-
PKA-sp1 dependent pathway to up-regulate expression of the protease inhibitor,
PN-1, at the transcriptional level. PN-1 resides in the Golgi apparatus and stabi-
lizes degradation of secretory granule proteins which are constantly turning over
at steady state. As a result, the increased secretory granule protein levels then
induce more granule formation.
6 Serpinin and pGlu-Serpinin Peptides Protect
against Cell Death
Serpinin and pGlu-serpinin peptides have been found to protect endocrine cells and
neurons against oxidative stress and cell death. Both these peptides reduced the
induced cytotoxicity in endocrine AtT20 cells, with pGlu-serpinin being 10-fold
more potent than serpinin (Fig. 10 ; Koshimizu et al. 2011b). pGlu-serpinin was also
found to be effective in protecting cortical neurons against H 2 O 2 induced oxidative
Fig. 7 Chromogranin A (CgA) levels directly affect dense core secretory granule numbers. (A)
Schematic describing the construction of antisense vectors for silencing CgA expression in AtT20
cells. (B) Western blot analysis of CgA in WT AtT20 cells and AtT20 cells treated with antisense
vectors. Note the different levels of silencing of CgA expression in the different clones (#5, #17,
#20) (C) Electron micrograph of WT AtT20 cells and AtT20-CgA antisense clone #5. Note the
apparent absence of dense core secretory granules in the antisense cells. (D) Quantification of
dense core granule formation in WT and CgA antisense AtT20 cells derived from electron micro-
graphs. Note the correlation of CgA levels and dense core granule numbers in the WT and anti-
sense treated clones (From Kim et al. 2001 )
Y. PengfiLoh et al.