Matches in SemOpenAlex for { <https://semopenalex.org/work/W2611885710> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W2611885710 endingPage "70" @default.
- W2611885710 startingPage "70" @default.
- W2611885710 abstract "Improved understanding of the regulation of contractions of uterine smooth muscle (myometrium) is essential to develop more successful strategies for prevention of premature birth, which remains the most common cause of infant death and disability. Oxytocin (OT) and prostaglandin (PG) F2a are potent myometrial stimulants which induce an increase in intracellular Ca++. This activates myosin light chain kinase (MLCK) and subsequently the cell’s contractile machinery. However, there is poor correlation between the rise in Ca++ and the strength of the myometrial contraction. Contractile strength greatly increases at the time of parturition partly due to Ca++-independent factors that sensitize the muscle to the rise in intracellular Ca++. In vascular smooth muscle, one key regulator in this process of Ca++ sensitization is the monomeric G-protein, RhoA which in turn activates Rho-associated kinase (ROK). Studies in the rat myometrium have shown that RhoA and ROK are involved in enhancing OT-induced contractions. The potential role of the RhoA/ROK system in uterine contractility at the time of parturition has not been investigated in the human myometrium or in human cell lines. 
 We propose to investigate the role of RhoA/ROK in the human myometrium using molecular cloning techniques. We have constructed expression plasmids for wild type, dominant positive (constitutively active), and dominant negative (constitutively inactive) isoforms of RhoA and synthesized purified proteins using a bacterial (BL21) translation system. These constructs will be introduced into primary and immortalized human myocytes using the protein transduction domain (TAT) derived from the HIV virus, which is capable of introducing whole proteins into mammalian cells. RhoA activation/translocation to the plasma membrane will be visualized using real time confocal microscopy in experiments where the RhoA proteins have been tagged with green fluorescent protein (GFP). Following introduction of the normal and mutant G-proteins, the downstream targets of activated ROK will be assayed for phosphorylation status using near infrared (NIR) fluorescence imaging of western blots or in-cell westerns. These targets include the myosin binding subunit (MBS) of myosin light chain phosphatase (MLCP), and two peptide phosphatase inhibitors of MLCP, CPI-17 and PHI-1. In addition, we propose to measure ROK activity directly using a direct enzyme assay. We will monitor calcium transients using fluorescence microscopy to verify the calcium independence of our measurements. These experiments will determine the role of the RhoA/ROK system in the mechanisms that may determine human uterine contractility. This information may direct new strategies to prevent or treat preterm labour." @default.
- W2611885710 created "2017-05-12" @default.
- W2611885710 creator A5038442760 @default.
- W2611885710 creator A5086686812 @default.
- W2611885710 date "2007-08-01" @default.
- W2611885710 modified "2023-10-18" @default.
- W2611885710 title "The role of THOA in calcium sensitization in human myometrial smooth muscles" @default.
- W2611885710 doi "https://doi.org/10.25011/cim.v30i4.2836" @default.
- W2611885710 hasPublicationYear "2007" @default.
- W2611885710 type Work @default.
- W2611885710 sameAs 2611885710 @default.
- W2611885710 citedByCount "0" @default.
- W2611885710 crossrefType "journal-article" @default.
- W2611885710 hasAuthorship W2611885710A5038442760 @default.
- W2611885710 hasAuthorship W2611885710A5086686812 @default.
- W2611885710 hasConcept C126322002 @default.
- W2611885710 hasConcept C134018914 @default.
- W2611885710 hasConcept C181080969 @default.
- W2611885710 hasConcept C184235292 @default.
- W2611885710 hasConcept C185592680 @default.
- W2611885710 hasConcept C201800478 @default.
- W2611885710 hasConcept C2777093181 @default.
- W2611885710 hasConcept C2778164554 @default.
- W2611885710 hasConcept C2779066055 @default.
- W2611885710 hasConcept C39133596 @default.
- W2611885710 hasConcept C62478195 @default.
- W2611885710 hasConcept C6997183 @default.
- W2611885710 hasConcept C71924100 @default.
- W2611885710 hasConcept C79879829 @default.
- W2611885710 hasConcept C8035138 @default.
- W2611885710 hasConcept C86803240 @default.
- W2611885710 hasConcept C95444343 @default.
- W2611885710 hasConcept C97029542 @default.
- W2611885710 hasConceptScore W2611885710C126322002 @default.
- W2611885710 hasConceptScore W2611885710C134018914 @default.
- W2611885710 hasConceptScore W2611885710C181080969 @default.
- W2611885710 hasConceptScore W2611885710C184235292 @default.
- W2611885710 hasConceptScore W2611885710C185592680 @default.
- W2611885710 hasConceptScore W2611885710C201800478 @default.
- W2611885710 hasConceptScore W2611885710C2777093181 @default.
- W2611885710 hasConceptScore W2611885710C2778164554 @default.
- W2611885710 hasConceptScore W2611885710C2779066055 @default.
- W2611885710 hasConceptScore W2611885710C39133596 @default.
- W2611885710 hasConceptScore W2611885710C62478195 @default.
- W2611885710 hasConceptScore W2611885710C6997183 @default.
- W2611885710 hasConceptScore W2611885710C71924100 @default.
- W2611885710 hasConceptScore W2611885710C79879829 @default.
- W2611885710 hasConceptScore W2611885710C8035138 @default.
- W2611885710 hasConceptScore W2611885710C86803240 @default.
- W2611885710 hasConceptScore W2611885710C95444343 @default.
- W2611885710 hasConceptScore W2611885710C97029542 @default.
- W2611885710 hasIssue "4" @default.
- W2611885710 hasLocation W26118857101 @default.
- W2611885710 hasOpenAccess W2611885710 @default.
- W2611885710 hasPrimaryLocation W26118857101 @default.
- W2611885710 hasRelatedWork W1556045283 @default.
- W2611885710 hasRelatedWork W2007560067 @default.
- W2611885710 hasRelatedWork W2028822365 @default.
- W2611885710 hasRelatedWork W2085795294 @default.
- W2611885710 hasRelatedWork W2111362194 @default.
- W2611885710 hasRelatedWork W2121139712 @default.
- W2611885710 hasRelatedWork W2611885710 @default.
- W2611885710 hasRelatedWork W2745603330 @default.
- W2611885710 hasRelatedWork W2749121481 @default.
- W2611885710 hasRelatedWork W3201165634 @default.
- W2611885710 hasVolume "30" @default.
- W2611885710 isParatext "false" @default.
- W2611885710 isRetracted "false" @default.
- W2611885710 magId "2611885710" @default.
- W2611885710 workType "article" @default.