Physiology Commons^™

Reactive Oxygen Species Mediate Tnfr1 Increase After Trpv1 Activation In Mouse Drg Neurons, Fei Ma, Liping Zhang, Karin N. Westlund

Physiology Faculty Publications

Background: Transient receptor potential vanilloid subtype 1 (TRPV1) is activated by low pH/protons and is well known to be involved in hyperalgesia during inflammation. Tumor necrosis factor α (TNF-α), a proinflammatory cytokine, is involved in nociceptive responses causing hyperalgesia through TNF receptor type 1 (TNFR1) activation. Reactive oxygen species (ROS) production is also prominently increased in inflamed tissue. The present study investigated TNFR1 receptors in primary cultured mouse dorsal root ganglion (DRG) neurons after TRPV1 activation and the involvement of ROS. C57BL/6 mice, both TRPV1 knockout and wild type, were used for immunofluorescent and live cell imaging. The L4 and …

Lrp1 Shedding In Human Brain: Roles Of Adam10 And Adam17, Qiang Liu, Juan Zhang, Hien Tran, Marcel M. Verbeek, Karina Reiss, Steven Estus, Guojun Bu

Physiology Faculty Publications

BACKGROUND: The low-density lipoprotein receptor-related protein 1 (LRP1) plays critical roles in lipid metabolism, cell survival, and the clearance of amyloid-beta (Abeta) peptide. Functional soluble LRP1 (sLRP1) has been detected in circulating human placenta; however, whether sLRP1 is also present in the central nervous system is unclear.

RESULTS: Here we show that abundant sLRP1 capable of binding its ligands is present in human brain tissue and cerebral spinal fluid (CSF). Interestingly, the levels of sLRP1 in CSF are significantly increased in older individuals, suggesting that either LRP1 shedding is increased or sLRP1 clearance is decreased during aging. To examine potential …

Adaptation And Mal-Adaptation To Ambient Hypoxia; Andean, Ethiopian And Himalayan Patterns, Guoqiang Xing, Clifford Qualls, Luis Huicho, Maria Rivera-Ch, Tsering Stobdan, Marat Slessarev, Eitan Prisman, Shoji Ito, Hong Wu, Angchuk Norboo, Diskit Dolma, Moses Kunzang, Tsering Norboo, Jorge L Gamboa, Victoria E. Claydon, Joseph Fisher, Guta Zenebe, Amha Gebremedhin, Roger Hainsworth, Ajay Verma, Otto Appenzeller

Physiology Faculty Publications

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of "fitness" for survival and the genetics that influence this are best carried out in the field and in matching environments.

Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment.

Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the …

Enkephalin-Encoding Herpes Simplex Virus-1 Decreases Inflammation And Hotplate Sensitivity In A Chronic Pancreatitis Model, Hong Yang, Terry A. Mcnearney, Rong Chu, Ying Lu, Yong Ren, David C. Yeomans, Steven P. Wilson, Karin N. Westlund

Physiology Faculty Publications

Background: A chronic pancreatitis model was developed in young male Lewis rats fed a high-fat and alcohol liquid diet beginning at three weeks. The model was used to assess time course and efficacy of a replication defective herpes simplex virus type 1 vector construct delivering human cDNA encoding preproenkephalin (HSV-ENK).

Results: Most surprising was the relative lack of inflammation and tissue disruption after HSV-ENK treatment compared to the histopathology consistent with pancreatitis (inflammatory cell infiltration, edema, acinar cell hypertrophy, fibrosis) present as a result of the high-fat and alcohol diet in controls. The HSV-ENK vector delivered to the pancreatic surface …

Gender-Specific Effects Of Hiv Protease Inhibitors On Body Mass In Mice, Melinda E. Wilson, Kimberly F. Allred, Elizabeth M. Kordik, Deana K. Jasper, Amanda N. Rosewell, Anthony J. Bisotti

Physiology Faculty Publications

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density …

The Pulmonary Effects Of Intravenous Adenosine In Asthmatic Subjects, Nausherwan K. Burki, Mahmud Alam, Lu-Yuan Lee

Physiology Faculty Publications

BACKGROUND: We have shown that intravenous adenosine in normal subjects does not cause bronchospasm, but causes dyspnea, most likely by an effect on vagal C fibers in the lungs [Burki et al. J Appl Physiol 2005; 98:180-5]. Since airways inflammation and bronchial hyperreactivity are features of asthma, it is possible that intravenous adenosine may be associated with an increased intensity of dyspnea, and may cause bronchospasm, as noted anecdotally in previous reports.

METHODS: We compared the effects of placebo and 10 mg intravenous adenosine, in 6 normal and 6 asthmatic subjects.

RESULTS: Placebo injection had no significant (p > 0.05) effect …

The Generation And Function Of Soluble Apoe Receptors In The Cns, G. William Rebeck, Mary Jo Ladu, Steven Estus, Guojun Bu, Edwin J. Weeber

Physiology Faculty Publications

More than a decade has passed since apolipoprotein E4 (APOE-epsilon4) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein system integrates into the puzzle of AD etiology. The specific pathological actions of apoE4, methods of modulating apolipoprotein E4-associated risk, and possible roles of apoE in normal synaptic function are still being debated. These critical questions will never be fully answered without a complete understanding of the life cycle of the apolipoprotein receptors that mediate the uptake, signaling, and degradation of apoE. The present review will focus …

Shelling Out For Genomics, Timothy S. Mcclintock, Charles D. Derby

Physiology Faculty Publications

A report on the symposium 'Genomic and Proteomic Approaches to Crustacean Biology' held as part of the Society for Integrative and Comparative Biology 2006 Annual Meeting, Orlando, USA, 4-8 January 2006.

Cbfbeta Is A Facultative Runx Partner In The Sea Urchin Embryo, Anthony J. Robertson, Carrie Dickey-Sims, Andrew Ransick, Dawn E. Rupp, John J. Mccarthy, James A. Coffman

Physiology Faculty Publications

BACKGROUND: Runx proteins are developmentally important metazoan transcription factors that form a heterodimeric complex with the non-homologous protein Core Binding Factor beta (CBFbeta). CBFbeta allosterically enhances Runx DNA binding but does not bind DNA itself. We report the initial characterization of SpCBFbeta, the heterodimeric partner of SpRunt-1 from the sea urchin Stronylocentrotus purpuratus.

RESULTS: SpCBFbeta is remarkably similar to its mammalian homologues, and like them it enhances the DNA binding of the Runt domain. SpCBFbeta is entirely of zygotic provenance and its expression is similar that of SpRunt-1, accumulating globally at late blastula stage then later localizing to endoderm and …

Effects Of Dietary Curcumin Or N-Acetylcysteine On Nf-Kappab Activity And Contractile Performance In Ambulatory And Unloaded Murine Soleus, Mehran Farid, Michael B. Reid, Yi-Ping Li, Eric Gerken, William J. Durham

Physiology Faculty Publications

BACKGROUND: Unloading of skeletal muscle causes atrophy and loss of contractile function. In part, this response is believed to be mediated by the transcription factor nuclear factor-kappa B (NF-kappaB). Both curcumin, a component of the spice turmeric, and N-acetylcysteine (NAC), an antioxidant, inhibit activation of NF-kappaB by inflammatory stimuli, albeit by different mechanisms. In the present study, we tested the hypothesis that dietary curcumin or NAC supplementation would inhibit unloading-induced NF-kappaB activity in skeletal muscle and thereby protect muscles against loss of mass and function caused by prolonged unloading.

METHODS: We used hindlimb suspension to unload the hindlimb muscles of …

Fatigue Resistance Of Rat Extraocular Muscles Does Not Depend On Creatine Kinase Activity, Colleen A. Mcmullen, Katrin Hayeß, Francisco H. Andrade

Physiology Faculty Publications

BACKGROUND: Creatine kinase (CK) links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1) CK isoform expression and activity in rat extraocular muscles would be higher, and (2) the resistance of these muscles to fatigue would depend on CK activity.

RESULTS: We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in …

Runx-Dependent Expression Of Pkc Is Critical For Cell Survival In The Sea Urchin Embryo, Carrie Dickey-Sims, Anthony J. Robertson, Dawn E. Rupp, John J. Mccarthy, James A. Coffman

Physiology Faculty Publications

BACKGROUND: Runx transcription factors play critical roles in the developmental control of cell fate and contribute variously as oncoproteins and tumor suppressors to leukemia and other cancers. To discover fundamental Runx functions in the cell biology of animal development, we have employed morpholino antisense-mediated knockdown of the sea urchin Runx protein SpRunt-1. Previously we showed that embryos depleted of SpRunt-1 arrest development at early gastrula stage and underexpress the conventional protein kinase C SpPKC1.

RESULTS: We report here that SpRunt-1 deficiency leads to ectopic cell proliferation and extensive apoptosis. Suppression of the apoptosis by pharmacological inhibition of caspase-3 prevents the …

Hiv Protease Inhibitors Promote Atherosclerotic Lesion Formation Independent Of Dyslipidemia By Increasing Cd36-Dependent Cholesteryl Ester Accumulation In Macrophages, James Dressman, Jeanie Kincer, Sergey V. Matveev, Ling Guo, Richard N. Greenberg, Theresa Guerin, David Meade, Xiang-An Li, Weifei Zhu, Annette M. Uittenbogaard, Melinda E. Wilson, Eric J. Smart

Physiology Faculty Publications

Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor–dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor–induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and …