This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The association between tobacco use and HIV/AIDS epidemics represents an area of growing clinical and public health importance. The present application focuses on a novel interaction between the HIV-1 envelope neurotoxin gp120, the a7 nicotinic acetylcholine receptor (a7 nAChR), and nicotine. HIV seropositive smokers display higher viral loads and lower CD4+ cell counts than HIV seropositive nonsmokers (Wojna et al., 2007) which may be the result of chronic activation of the upregulated a7 nAChR (due to gp120 chronic exposure) in immune cells by nicotine which could lead to calcium overloading of immune cells and ultimately apoptosis. We hypothesize that drugs which interefere with the a7 nAChR functionality could potentially alleviate the pathological consequences that may result from the chronic nicotine stimulation of the upregulated a7 nAChR. The long-term goal of these studies is to define whether a smoking cessation therapy based on the use of a nicotinic receptor antagonist will improve the immunological profile of HIV-seropositive smokers and to investigate whether smoking cessation medication can be used as adjunctive therapy during HIV infection. The rationale for using antagonists is that by interfering with the upregulated a7 nAChR activity, antagonists are expected to reduce calcium overloading and the potentially related apoptosis. Bupropion will be studied as a model a7 nAChR antagonist. Our extensive experience in the study of nAChRs and MDMs, our established expertise in confocal imaging and electrophysiological techniques, and our strong collaborations with clinicians from the NeuroAIDS Program at UPR-MSC place us in a priviledged position to carry out the proposed studies successfully and complete the work in a timely manner. We propose the following aims: (1) To elucidate whether a7 nAChR antagonist bupropion protects MDMs against calcium overloading due to gp120 exposure, (2) To determine the effects of bupropion on agonist-induced single-channel ?7 nAChR currents in MDMs, and (3) To correlate the gp120-induced ?7 nAChR upregulation in MDMs with apoptosis using flow cytometry and determine whether bupropion at therapeutic concentrations protects against apoptosis.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54RR026139-02
Application #
8359917
Study Section
Special Emphasis Panel (ZRR1-RI-1 (02))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$166,320
Indirect Cost
Name
University of Puerto Rico Med Sciences
Department
Type
Schools of Medicine
DUNS #
948108063
City
San Juan
State
PR
Country
United States
Zip Code
00936
Ortiz, A P; Tamayo, V; Scorsone, A et al. (2017) Prevalence and correlates of cervical HPV infection in a clinic-based sample of HIV-positive Hispanic women. Papillomavirus Res 4:39-44
Jimenez-Torres, Gladys J; Wojna, Valerie; Rosario, Ernesto et al. (2017) Assessing health-related resiliency in HIV+ Latin women: Preliminary psychometric findings. PLoS One 12:e0181253
Joshipura, Kaumudi J; Muñoz-Torres, Francisco J; Campos, Maribel et al. (2017) Association between within-visit systolic blood pressure variability and development of pre-diabetes and diabetes among overweight/obese individuals. J Hum Hypertens 32:26-33
Maldonado-Martínez, Gerónimo; Hunter-Mellado, Robert F; Fernández-Santos, Diana et al. (2016) Persistent HIV Viremia: Description of a Cohort of HIV Infected Individuals with ART Failure in Puerto Rico. Int J Environ Res Public Health 13:ijerph13010050
Soto-Salgado, Marievelisse; Colón-López, Vivian; Perez, Cynthia et al. (2016) Same-Sex Behavior and its Relationship with Sexual and Health-Related Practices Among a Population-Based Sample of Women in Puerto Rico: Implications for Cancer Prevention and Control. Int J Sex Health 28:296-305
Mas Rodriguez, Manuel F; Berrios, Rafael Arias; Ramos, Edwardo (2016) Spontaneous Bilateral Vertebral Artery Dissection During a Basketball Game: A Case Report. Sports Health 8:53-6
Colón-López, Vivian; Toro-Mejías, Lizbeth M; Conde-Toro, Alexandra et al. (2016) Views on HPV and HPV Vaccination: The Experience at a Federal Qualified Clinic in Puerto Rico. J Health Care Poor Underserved 27:1411-26
Valderrábano, Rodrigo J; Blanco, Alejandro; Santiago-Rodriguez, Eduardo J et al. (2016) Risk factors and clinical outcomes of arrhythmias in the medical intensive care unit. J Intensive Care 4:9
Silva, Frieda; Martin, Ralph J; Figueroa, Jannette et al. (2016) Variability of Serum Thyroglobulin Levels in Post- Thyroidectomy Patients with Well-Differentiated Thyroid Cancer: the ATA Guidelines. P R Health Sci J 35:142-6
Díaz-Santana, Mary Vanellys; Suárez Pérez, Erick L; Ortiz Martínez, Ana P et al. (2016) Association Between the Hypertriglyceridemic Waist Phenotype, Prediabetes, and Diabetes Mellitus Among Adults in Puerto Rico. J Immigr Minor Health 18:102-9

Showing the most recent 10 out of 133 publications