Medical Physiology Commons^™

Causality Analysis And Cell Network Modeling Of Spatial Calcium Signaling Patterns In Liver Lobules., Aalap Verma, Anil Noronha Antony, Babatunde A. Ogunnaike, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Dynamics as well as localization of Ca2+ transients plays a vital role in liver function under homeostatic conditions, repair, and disease. In response to circulating hormonal stimuli, hepatocytes exhibit intracellular Ca2+ responses that propagate through liver lobules in a wave-like fashion. Although intracellular processes that control cell autonomous Ca2+ spiking behavior have been studied extensively, the intra- and inter-cellular signaling factors that regulate lobular scale spatial patterns and wave-like propagation of Ca2+ remain to be determined. To address this need, we acquired images of cytosolic Ca2+ transients in 1300 hepatocytes situated across several mouse liver lobules over a period of …

Propofol Inhibits The Voltage-Gated Sodium Channel Nachbac At Multiple Sites., Yali Wang, Elaine Yang, Marta M. Wells, Vasyl Bondarenko, Kellie Woll, Vincenzo Carnevale, Daniele Granata, Michael L. Klein, Roderic G. Eckenhoff, William P. Dailey, Manuel Covarrubias, Pei Tang, Yan Xu

Department of Neuroscience Faculty Papers

Voltage-gated sodium (Na_V) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic Na_V channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects …

High Fat Diet Upregulates Fatty Acid Oxidation And Ketogenesis Via Intervention Of Ppar-Γ., Kunal Sikder, Sanket Kumar Shukla, Neel Patel, Harpreet Singh, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis.

METHODS: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy. Treatment course was followed by echocardiographic measurements, glycemic and …