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Expression Profile and Subcellular Localization of GAPDH in the Smooth Muscle Cells of Human Atherosclerotic Plaque: An Immunohistochemical and Ultrastructural Study with Biological Therapeutic Perspectives

Published online by Cambridge University Press:  23 May 2014

Ida Perrotta ,
Saveria Aquila  and
Sergio Mazzulla
Ida Perrotta*
Affiliation:
Department of Biology, Ecology and Earth Science (Di.B.E.S.T.), University of Calabria – Arcavacata, Rende 87036, Cosenza, Italy
Saveria Aquila
Affiliation:
Centro Sanitario – Department of Pharmacy and Sciences of Health and Nutrition, University of Calabria – Arcavacata, Rende 87036, Cosenza, Italy
Sergio Mazzulla
Affiliation:
Department of Biology, Ecology and Earth Science (Di.B.E.S.T.), University of Calabria – Arcavacata, Rende 87036, Cosenza, Italy
*
*Corresponding author. [email protected]
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Abstract

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been considered a classical glycolytic enzyme involved exclusively in cytosolic energy production. Several recent studies, however, have demonstrated that GAPDH is a multifunctional protein whose presence and activity can be regulated by disease states and/or experimental manipulation. Expression levels of GAPDH have been shown to be altered in certain tumors as well as in proliferating and differentiating cells. Since dedifferentiation and proliferation of smooth muscle cells (SMCs) are important features of human atherosclerosis, we have characterized the expression profile of GAPDH in the SMCs of atherosclerotic plaques and its putative interrelationship with the synthetic/proliferative status of these cells utilizing the proliferating cell nuclear antigen (PCNA) antibody, a valuable marker of cell proliferation. Western blot data revealed that GAPDH was significantly upregulated in atherosclerotic plaque specimens. Immunohistochemical stains demonstrated that GAPDH accumulated in the nucleus of dedifferentiated SMCs that also showed positive immunoreactivity for PCNA, but remained cytoplasmatic in the contractile SMCs (PCNA-negative), thus reflecting the proliferative, structural and synthetic differences between them. We suggest that, in human atherosclerotic plaque, GAPDH might exert additional functions that are independent of its well-documented glycolytic activity and might play key roles in development of the disease.

Keywords

atherosclerosisGAPDHproliferating SMCselectron microscopygene expressioncellular localization
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 20 , Issue 4 , August 2014 , pp. 1145 - 1157
Copyright
© Microscopy Society of America 2014 

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