Effect of Shz-1, a Cardiogenic Small Molecule, on Expression of Tropomyosin in Axolotl Heart

Author(s)

Dipak K. Dube , Sowmya Pinnamaneni , Syamalima Dube , Caitlin Welch , Runa Shrestha , Patricia M. Benz , Lynn Abbott , Bernard J. Poiesz ,

Download Full PDF Pages: 24-40 | Views: 922 | Downloads: 227 | DOI: 10.5281/zenodo.3408082

Volume 2 - April 2013 (04)

Abstract

A family of sulfonyl-hydrazone (Shz) small molecules including shz-1 was found to induce Nkx2.5 gene and subsequently -tropomyosin in P19CL6 cells. In order to understand the mechanism by which shz-1 ropomyosin , we employed Mexican axolotl ( Ambystoma mexicanum ) as the animal model, which we use in our laboratory for studying the structural/functional relationship of tropomyosin in relation to cardiogenesis and cardiac myofibrillogenesis. Tropomyosins are a family of actin binding proteins that show cell specific diversity by a combination of multiple genes and alternative RNA splicing. Of the 4 tropomyosin genes, both TPM1 and TPM4 genes play pivotal roles in myofibrillogenesis as well as cardiac cointraperitoneally into juvenile axolotl, shz-1 augmented texpression of TPM2 transcript was also increased. HOWEVER, TPM3 and cardiac TnT expression remained unchanged. In contrast to transcript expression, our western blot analysis with sarcomeric tropomyosin-specific antibodies did not show any significant increase in tropomyosin expression in shz-1 treated striated muscles. Similarly, western blot analysis with extracts of whole embryos failed to record any increases in tropomyosin expression in embryos maintained for four days in the presence or absence of 5-1. The contradictory results of transcript analysis by RT-PCR and protein analysis by western blotting strongly suggest that sarcomeric tropomyosin transcripts in axolotl heart may undergo translational control similar to that had been proposed in t-ablated mice.

Keywords

Ambystoma mexicanum, Shz-1, Nkx2.5, sarcomeric tropomyosin, gene expression

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