Role of Gap Junction Protein Connexin43 in Cell Proliferation

Thomas, Deepthi (2017) Role of Gap Junction Protein Connexin43 in Cell Proliferation. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (MS dissertation of Deepthi Thomas (12MS011)) DEEPTHI_THOMAS_12MS011_DBS.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

Cx43 is the dominant gap junction protein in brain, where it is found primarily between astrocytes. Astrocytes are well connected through Cx43 mediated Gap junction channels (GJCs) forming a panglial network and helps in maintaining metabolic homeostasis and osmotic balance. The disruption of cell to cell communication can result in uncontrolled cell growth, often leading to cancer. 4-Phenylbutyrate (4-PBA) is a histone deacetylase inhibitor which increases gene transcription by helping transcription factors to gain access to specific regions of DNA. Very recently in one of our studies we have observed that 4-PBA enhances gap junction intercellular communication (GJIC) in Mouse Hepatitis Virus (MHV) infected primary astrocytes by increasing the surface level expression of the gap junction protein Connexin 43 (Cx43).This study is focused to understand whether 4-PBA can increase the gap junction communication mediated through Cx43 in Delayed Brain Tumor (DBT) astrocytoma cells and to see if the improved functional coupling of tumor cells has any role in cell cycle progression and cell growth. Findings from the study revealed that 4-PBA increases surface level expression of Cx43 by trafficking Cx43 to the cell surface which in turn enhances functional gap junction coupling in vitro in a dose dependent manner. Also in DBT cells 10mM4-PBA caused a delay in cell cycle progression. Also we showed that p53 level remain unchanged after treatment suggesting the cell cycle delay could be induced via p53 independent mechanisms.

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