Life Sciences Commons^™

Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam

Dissertations & Theses (Open Access)

ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …

Astrocytes Rescue Neuronal Health After Cisplatin Treatment Through Mitochondrial Transfer., Krystal English, Krystal English

Dissertations & Theses (Open Access)

Abstract

Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer.

Author: Krystal English

Advisory Professor: Dr. Cobi J. Heijnen, Ph.D.

Chemotherapy-induced cognitive impairments are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially, mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health.

We used an in vitro system in which astrocytes with Mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons or neuronal stem …

Gating Mechanisms Of The Canonical Trp Channel Isoform Trpc4, Dhananjay P. Thakur

Dissertations & Theses (Open Access)

Non-selective cation channels formed by Transient Receptor Potential Canonical (TRPC) proteins play important roles in regulatory and pathophysiological processes. These channels are known to be activated downstream from phospholipase C (PLC) signaling. However, the mechanism by which the PLC pathway activates TRPC4/C5 remains unclear. Uniquely, TRPC4 is maximally activated only when two separate G protein pathways, G_q/11 and G_i/o, are co-stimulated, making it a coincidence detector of G_q/11- and G_i/o -coupled receptor activation. Using HEK293 cells co-expressing mouse TRPC4β and selected G protein-coupled receptors, I observed that coincident stimulation of G_i/o proteins and …

Regulation Of Functional Expression Of Mechanosensitive Trpv4 Channel In The Distal Nephron By Dietary Potassium And Sodium Intake, Nabila Boukelmoune

Dissertations & Theses (Open Access)

The Ca²⁺-permeable TRPV4 channel is predominantly expressed in the distal nephron (DN) and its activity is essential for [Ca²⁺]_i elevations in response to increased tubular flow. Here, I probed the physiological mechanisms controlling TRPV4 function and expression in the DN. I found that renal TRPV4 expression and mRNA levels were significantly increased by high K⁺ diet (5%) and decreased by dietary K⁺ restriction (0.003%). In contrast, variations in Na⁺ regimen had no apparent effect on TRPV4 expression and mRNA levels. Regulation of TRPV4 protein expression by K⁺ diet was independent of …

Role Of Neurogranin In The Regulation Of Calcium Binding To Calmodulin, Anuja Chandrasekar

Dissertations & Theses (Open Access)

Role of Neurogranin in the regulation of calcium binding to Calmodulin

Anuja Chandrasekar, B.S

Advisor: M. Neal Waxham, Ph.D

The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, …

Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout

Dissertations & Theses (Open Access)

Traumatic brain injury (TBI) often results in disruption of the blood brain barrier (BBB), which is an integral component to maintaining the central nervous system homeostasis. Recently cytosolic calcium levels ([Ca²⁺]i), observed to elevate following TBI, have been shown to influence endothelial barrier integrity. However, the mechanism by which TBI-induced calcium signaling alters the endothelial barrier remains unknown. In the present study, an in vitro BBB model was utilized to address this issue. Exposure of cells to biaxial mechanical stretch, in the range expected for TBI, resulted in a rapid cytosolic calcium increase. Modulation of intracellular and extracellular …