Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth

Background: Preterm labour is linked to higher mortality and morbidity rates. It has many possible causes; however the vast majority are idiopathic. Current pharmacological interventions are ineffective in reducing preterm birth rates and the associated mortality and morbidity. In order to progress,...

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Main Author: Thompson, Nicolette
Format: Dissertation (University of Nottingham only)
Language:English
Published: 2009
Online Access:https://eprints.nottingham.ac.uk/23437/
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author Thompson, Nicolette
author_facet Thompson, Nicolette
author_sort Thompson, Nicolette
building Nottingham Research Data Repository
collection Online Access
description Background: Preterm labour is linked to higher mortality and morbidity rates. It has many possible causes; however the vast majority are idiopathic. Current pharmacological interventions are ineffective in reducing preterm birth rates and the associated mortality and morbidity. In order to progress, research into the biological and molecular processes occurring in pregnancy and labour has been highlighted. Tissue transglutaminase 2 (TGII) inhibition inhibits contractions, leading onto questions about this multifunction protein’s role in pregnancy and labour Aims: 1. To determine TGII protein expression in human myometrium during non-pregnancy, pregnancy and labour. 2. To determine α-actin and α-tubulin expression in human myometrium during non-pregnancy, pregnancy and labour. 3. To determine the sub-cellular localisation of TGII, α-actin and α-tubulin in cells derived from pregnant non-labouring myometrium. 4. To determine whether TGII co-localises with either α-actin or α-tubulin in cells derived from pregnant non-labouring myometrium. Participants: tissue samples of smooth muscle myometrium were collected from women undergoing elective/emergency caesarean sections or hysterectomies. The three groups were non-pregnant, term-not-in-labour and term-in-labour. Design: Western blotting and related methodologies were carried out to determine TGII, α-actin and α-tubulin levels across the three sample groups. Immunocytocehmistry and related methodologies were carried out to determine the sub-cellular locations of TGII, α-actin and α-tubulin and whether TGII co-localised with either of the cytoskeletal proteins. Results: Significance was found in TGII levels between non-pregnant and term-not-in-labour (p≤0.05) and term-in-labour (p≤0.01). No significant difference was found in cytoskeletal protein levels. TGII subcellular location in pregnant non-labouring cells was cytoplasmic, indicating TGase activity not GTPase activitiy. No significant co-localisation was found between TGII and either α-actin and α-tubulin. Conclusion: Pregnancy has an impact on the expression of TGII. TGII role in regulating contractility is not through the result of co-localisation with α-actin and α-tubulin. Its mechanism in inhibiting contractions remains unclear.
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spelling nottingham-234372018-02-17T20:45:44Z https://eprints.nottingham.ac.uk/23437/ Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth Thompson, Nicolette Background: Preterm labour is linked to higher mortality and morbidity rates. It has many possible causes; however the vast majority are idiopathic. Current pharmacological interventions are ineffective in reducing preterm birth rates and the associated mortality and morbidity. In order to progress, research into the biological and molecular processes occurring in pregnancy and labour has been highlighted. Tissue transglutaminase 2 (TGII) inhibition inhibits contractions, leading onto questions about this multifunction protein’s role in pregnancy and labour Aims: 1. To determine TGII protein expression in human myometrium during non-pregnancy, pregnancy and labour. 2. To determine α-actin and α-tubulin expression in human myometrium during non-pregnancy, pregnancy and labour. 3. To determine the sub-cellular localisation of TGII, α-actin and α-tubulin in cells derived from pregnant non-labouring myometrium. 4. To determine whether TGII co-localises with either α-actin or α-tubulin in cells derived from pregnant non-labouring myometrium. Participants: tissue samples of smooth muscle myometrium were collected from women undergoing elective/emergency caesarean sections or hysterectomies. The three groups were non-pregnant, term-not-in-labour and term-in-labour. Design: Western blotting and related methodologies were carried out to determine TGII, α-actin and α-tubulin levels across the three sample groups. Immunocytocehmistry and related methodologies were carried out to determine the sub-cellular locations of TGII, α-actin and α-tubulin and whether TGII co-localised with either of the cytoskeletal proteins. Results: Significance was found in TGII levels between non-pregnant and term-not-in-labour (p≤0.05) and term-in-labour (p≤0.01). No significant difference was found in cytoskeletal protein levels. TGII subcellular location in pregnant non-labouring cells was cytoplasmic, indicating TGase activity not GTPase activitiy. No significant co-localisation was found between TGII and either α-actin and α-tubulin. Conclusion: Pregnancy has an impact on the expression of TGII. TGII role in regulating contractility is not through the result of co-localisation with α-actin and α-tubulin. Its mechanism in inhibiting contractions remains unclear. 2009-07 Dissertation (University of Nottingham only) NonPeerReviewed application/pdf en https://eprints.nottingham.ac.uk/23437/1/Nicolette_Thompson_pdf.pdf Thompson, Nicolette (2009) Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth. [Dissertation (University of Nottingham only)] (Unpublished)
spellingShingle Thompson, Nicolette
Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth
title Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth
title_full Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth
title_fullStr Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth
title_full_unstemmed Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth
title_short Tissue Transglutaminase 2 (TGII), Its Protein Expression and Possible Role in Cytoskeletal Regulation during Pregnancy with Applications to Preterm Birth
title_sort tissue transglutaminase 2 (tgii), its protein expression and possible role in cytoskeletal regulation during pregnancy with applications to preterm birth
url https://eprints.nottingham.ac.uk/23437/