TY - JOUR
T1 - Distribution of proSAAS-derived peptides in rat neuroendocrine tissues
AU - Feng, Y.
AU - Reznik, S. E.
AU - Fricker, L. D.
N1 - Funding Information:
This work was supported in part by the U.S. National Institutes of Health Grants R01 DA-04494 (L.D.F.), K02 DA-00194 (L.D.F.), and K08 HD-01209 (S.E.R.). Thanks to Dr. James Douglass and his colleagues at Amgen for the gift of rabbit antisera to PEN and LEN, to Dr. Iris Lindberg (Louisiana State University Medical Center) for the gift of the C-terminal peptide corresponding to PC1 for the generation of guinea-pig antiserum, and to Dr. Lakshmi Devi (New York University School of Medicine) for the rabbit antiserum to PC1 and for helpful advice.
PY - 2001/7/27
Y1 - 2001/7/27
N2 - Using a technique to identify substrates of the peptide processing enzyme carboxypeptidase E (CPE), several novel peptides were detected in the brain and pituitary of Cpefat/Cpefat mice and found to be derived from a single precursor, termed proSAAS. In order to gain further information regarding the potential physiological roles of these peptides, we have examined the distribution of two proSAAS-derived peptides, ARPVKEPRSLSAASAPLAETSTPLRL (SAAS) and LENSSPQAPARRLLPP (LEN), in rat neuroendocrine tissues using immunohistochemistry. Both peptides are detected throughout the brain, with the highest concentrations of SAAS peptide in the hypothalamus. In the hippocampus, both peptides are co-localized with prohormone convertase 1 in the dentate gyrus and CA1-3 region. In cerebellum, SAAS peptide is co-localized with prohormone convertase 1 in Purkinje and granular cells, whereas LEN is much more abundant in the Purkinje cells relative to the granular cells. Similarly, SAAS and prohormone convertase 1 are co-localized in the dorsal horn of the spinal cord, while LEN is mainly restricted to fibers of the white matter. In the pituitary, SAAS, LEN, and prohormone convertase 1 are detected in all three lobes. In the pancreas, SAAS, LEN, and prohormone convertase 1 are only detected in the islets, although the peptides are enriched in the peripheral cells (alpha and/or delta) while prohormone convertase 1 is only expressed in the inner cells (beta). Both SAAS and LEN are present in the adrenal medulla along with prohormone convertase 1. Taken together, these data are consistent with the proposed role for proSAAS as an endogenous inhibitor of prohormone convertase 1 in many, but not all cell types. However, the broader localization of the peptides allows for the possibility that they perform additional functions.
AB - Using a technique to identify substrates of the peptide processing enzyme carboxypeptidase E (CPE), several novel peptides were detected in the brain and pituitary of Cpefat/Cpefat mice and found to be derived from a single precursor, termed proSAAS. In order to gain further information regarding the potential physiological roles of these peptides, we have examined the distribution of two proSAAS-derived peptides, ARPVKEPRSLSAASAPLAETSTPLRL (SAAS) and LENSSPQAPARRLLPP (LEN), in rat neuroendocrine tissues using immunohistochemistry. Both peptides are detected throughout the brain, with the highest concentrations of SAAS peptide in the hypothalamus. In the hippocampus, both peptides are co-localized with prohormone convertase 1 in the dentate gyrus and CA1-3 region. In cerebellum, SAAS peptide is co-localized with prohormone convertase 1 in Purkinje and granular cells, whereas LEN is much more abundant in the Purkinje cells relative to the granular cells. Similarly, SAAS and prohormone convertase 1 are co-localized in the dorsal horn of the spinal cord, while LEN is mainly restricted to fibers of the white matter. In the pituitary, SAAS, LEN, and prohormone convertase 1 are detected in all three lobes. In the pancreas, SAAS, LEN, and prohormone convertase 1 are only detected in the islets, although the peptides are enriched in the peripheral cells (alpha and/or delta) while prohormone convertase 1 is only expressed in the inner cells (beta). Both SAAS and LEN are present in the adrenal medulla along with prohormone convertase 1. Taken together, these data are consistent with the proposed role for proSAAS as an endogenous inhibitor of prohormone convertase 1 in many, but not all cell types. However, the broader localization of the peptides allows for the possibility that they perform additional functions.
KW - 7B2
KW - Carboxypeptidase E
KW - Granin
KW - Peptide processing
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U2 - 10.1016/S0306-4522(01)00200-7
DO - 10.1016/S0306-4522(01)00200-7
M3 - Article
C2 - 11672612
AN - SCOPUS:0035958718
SN - 0306-4522
VL - 105
SP - 469
EP - 478
JO - Neuroscience
JF - Neuroscience
IS - 2
ER -