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Chromogranin A and Derived Peptides in Health and Disease

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Abstract

Chromogranin A (CgA) is a member of the granins, a family of acidic proteins found in abundance in (neuro)endocrine cells (e.g., in chromaffin cells) and in some tumors. Like other granins, CgA has a granulogenic role in secretory granule biogenesis and is stored in these organelles. CgA is partially processed differentially in various cell types to yield biologically active peptides, such as vasostatin, pancreastatin, catestatin, and serpinins. In this review, we describe the roles of CgA and several of its derived peptides. CgA, which is elevated in the blood of cancer patients, inhibits angiogenesis and exerts protective effects on the endothelial barrier function in tumors, thus affecting response to chemotherapy. Recent studies indicate that the serpinins promote cell survival and myocardial contractility and relaxation. Other peptides such as pancreastatin were found to have significant effects on inhibition of glucose-stimulated insulin secretion and glucose up-take, induction of glycogenolysis in hepatocytes, and inhibition of lipogenesis. In contrast, catestatin has opposite effects to that of pancreastatin in glucose metabolism and lipogenesis. Catestatin appears to also play a significant role in cardiac function, blood pressure regulation, and mutations in the catestatin domain of the CgA gene are associated with hypertension in humans.

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Abbreviations

ADD1:

Adipocyte determination and differentiation factor 1

BP:

Blood pressure

CST:

Catestatin

CVLM:

Caudal ventrolateral medulla

GLUT4:

Glucose transporter type 4

Gpat:

Glycerol-3-phosphate acyltransferase

MAP:

Mean arterial pressure

NO:

Nitric oxide

NTS:

Nucleus of the solitary tract

Ppar-γ:

Peroxisome proliferator-activated receptor gamma

ROS:

Reactive oxygen species

SNP:

Single nucleotide polymorphism

Srebp1c:

Sterol regulatory element-binding protein 1c

UTR:

Untranslated region

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Acknowledgments

We thank Dr. Niamh Cawley (NIH) for helpful discussions. This work was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA (YPL, YC). S.K.M. is supported by grants from the VA Merit Review and the National Institutes of Health. B.T. was supported by a grant from the University of Calabria (Cosenza), Italy. A.C. was supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC) of Italy.

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Authors and Affiliations

  1. Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    Y. Peng Loh & Yong Cheng

  2. VA San Diego Healthcare System, San Diego, CA, 92161, USA

    Sushil K. Mahata

  3. Department of Medicine (0838), University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0838, USA

    Sushil K. Mahata

  4. Tumor Biology and Vascular Targeting Unit, DIBIT-Division of Molecular Oncology, San Raffaele Scientific Institute, Milan, 20132, Italy

    Angelo Corti

  5. Department of Cell Biology, University of Calabria, Arcavacata di Rende (CS), 87030, Italy

    Bruno Tota

  6. National Institutes of Health, Bldg. 49, Room 5A22, Bethesda, MD, 20892, USA

    Y. Peng Loh

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  1. Y. Peng Loh
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  2. Yong Cheng
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Correspondence to Y. Peng Loh.

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Loh, Y.P., Cheng, Y., Mahata, S.K. et al. Chromogranin A and Derived Peptides in Health and Disease. J Mol Neurosci 48, 347–356 (2012). https://doi.org/10.1007/s12031-012-9728-2

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