Physiology Commons^™

Clinical Significance, Functional Role And Molecular Mechanism Of 2’-O-Methyltransferase Ftsj3 In Promoting Cancer Progression, Morenci Manning-Powell

Wayne State University Dissertations

2’-O-methylation (2’-O-Me), one of the most common modifications within RNA, has multiple roles in modulating RNA structure, stability, and interactions, as well as gene transcription and translation. We previously performed integrative genomic and transcriptomic analysis of 58 RNA methyltransferases, and identified FTSJ3 (FtsJ RNA 2ʹ-O-methyltransferase 3) as significantly amplified/overexpressed in breast cancer. Knockdown of FTSJ3 inhibits breast cancer cell growth in vitro. However, the clinical significance, functional role, and molecular mechanism of FTSJ3 in human cancer remains to be elucidated. In the present study, we first analyzed the differential mRNA and protein expression of FTSJ3 between tumor and normal tissues …

The Balance Between Prostaglandin E2 Ep3 And Ep4 Receptors Determines Severity Of Cardiac Damage In Myocardial Infarction And An Angiotensin Ii-Induced Model Of Hypertension, Timothy Dean Bryson

Wayne State University Dissertations

According to the center for disease control about 610,000 people die every year in the United States from heart disease, of which, coronary heart disease is the most common form. One major risk factor for heart attack is hypertension, which affects nearly half of all Americans [472, 473]. PGE2 plays an important role in regulating cardiovascular function and mediating inflammation, both of which contribute to the development of hypertension and/or heart disease. Prostaglandin E2 can act as a vasodilator or vasoconstrictor depending on which of its receptor subtypes are activated.

In general, activation of the EP1 and EP3 receptors is …

Appropriate Preconditioning Of The Uterine Endoplasmic Reticulum Stress Response Inhibits Preterm Labor, Judith Ann Ingles

Wayne State University Dissertations

Introduction: In this study, we are testing the overarching hypothesis that preconditioning the myometrial UPR allows for the maintenance of non-apoptotic CASP3 activity and thus sustains uterine quiescence. We have previously demonstrated that the pregnant uterus facilitates uterine quiescence through UPR mediated activation of non-apoptotic CASP3, yet the mechanism in which CASP3 utilizes to avoid its apoptotic cell fate is unresolved. There is a growing body of evidence including our own that demonstrates remote and direct preconditioning with minor stresses propagates cytoprotective mechanisms that allow for the avoidance of apoptotic cell death upon exposure to a subsequent more damaging stress, …

Role Of Alström Syndrome 1 (Alms1) In Nkcc2 Endocytosis, Thick Ascending Limb Function, Blood Pressure Regulation And Metabolic Function, Ankita Bachhawat Jaykumar

Wayne State University Dissertations

NaCl absorption by the Thick Ascending Limb (TAL) is mediated by the apical Na+/K+/2Cl- co-transporter, NKCC2. Increased NKCC2 activity and apical trafficking are associated to salt sensitive hypertension in rodents and humans. NKCC2 endocytosis is important for maintaining surface NKCC2 such that blocking NKCC2 endocytosis increased NKCC2 surface abundance and NKCC2-mediated NaCl reabsorption. Despite its importance, NKCC2 endocytosis has been poorly studied and a part of the reason may be attributed to the lack of availability of methods with good time resolution. Hence, we developed a method to image apical NKCC2 to monitor its endocytosis in real-time by Total Internal …

Regulation Of Nkcc2 Trafficking By Vesicle Fusion Proteins Vamp2 And Vamp3 In The Thick Ascending Limb, Paulo Sebastian Caceres Puzzella

Wayne State University Dissertations

The thick ascending limb (TAL) in the kidney regulates extracellular fluid volume and blood pressure. The Na/K/2Cl cotransporter NKCC2 plays a central role in NaCl absorption by the TAL and blood pressure. NKCC2 trafficking to the apical membrane is a major mechanism to control NKCC2 activity. However, little is known about the proteins that mediate NKCC2 trafficking. Inhibition of the vesicle fusion proteins VAMP2 and VAMP3 blunts the increase in surface NKCC2 expression and NaCl absorption in response to stimulation by cAMP. In other cells, VAMPs mediate fusion of exocytic vesicles with the plasma membrane. Whether VAMP2 and VAMP3 mediate …

Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong

Wayne State University Dissertations

Mitochondrial fusion and fission, collectively termed mitochondrial dynamics, are among the core mechanisms responsible for maintaining mitochondrial health and functional integrity. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. Recent studies suggest that i) mitochondrial dynamics, particularly, mitochondrial fission, serves as a mediator of cell fate in the setting of ischemia-reperfusion (IR) injury, and, ii) inhibition of DRP1 and mitochondrial fission provides cardioprotection against IR injury. However, the precise role of DRP1 translocation to mitochondria in the pathogenesis of myocardial ischemia-reperfusion injury has not been established.

Using an established model of hypoxia-reoxygenation (HR) in cultured HL-1 cardiomyocytes, …

Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman

Wayne State University Dissertations

Junctional SR is an important and unique ER subdomain in the adult myocyte that releases Ca2+ through the actions of an exclusive set of resident proteins. Cardiac calsequestrin (CSQ2) undergoes two co-translational modifications: N-linked glycosylation on 316Asn, and phosphorylation by protein kinase CK2 on a cluster of 3 serines in its tail. In the heart, CSQ2 molecules undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. To investigate CSQ2 protein processing in cardiomyopathy models, studies were performed to test whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced into …

Characterization Of High-Voltage-Activated Calcium Channels In Retinal Bipolar Cells, Qi Lu

Wayne State University Dissertations

Retinal bipolar cells, conveying visual information from photoreceptors to ganglion cells, segregate visual information into multiple parallel pathways through their diversified cell types and physiological properties. Voltage-gated Ca²⁺ channels could be particularly important underlying the diversified physiological properties of different BCs. In this dissertation, I investigated the high-voltage-activated (HVA) calcium current in retinal bipolar cells in mice. In the first part of my dissertation, I characterized multiple bipolar cell-expressing GFP and/or Cre transgenic mouse lines. In the second part of my dissertation, by performing whole-cell patch-clamp recordings, I examined the electrophysiological properties of HVA calcium currents among CBCs and …