Dr. Cynthia P. Saloma

Details

Sex: Female
Education:

Doctor of Philosophy in Physiology, Osaka University, 1998
Master of Medical Science, Physiology, Osaka University, 1995
Bachelor of Science in Molecular Biology, Nagoya University, 1993
Bachelor of Science in Fisheries, University of the Philippines Visayas, 1987

Field of Specialization:
Molecular Biology
Biotechnology
Genomics

Researches:

Article title: Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines
Authors: Francis A. Tablizo, Cynthia P. Saloma, Marc Jerrone R. Castro, Kenneth M. Kim, Maria Soﬁa L. Yangzon, Carlo M. Lapid, Benedict A. Maralit, Marc Edsel C. Ayes, Jan Michael C. Yap, Jo-Hannah S. Llames, Shiela Mae M. Araiza, Kris P. Punayan, Irish Coleen A. Asin, Candice Francheska B. Tambaoan, Asia Louisa U. Chong, Karol Sophia Agape R. Padilla, Rianna Patricia S. Cruz, El King D. Morado, Joshua Gregor A. Dizon, Eva Maria Cutiongco-de la Paz, Alethea R. de Guzman, Razel Nikka M. Hao, Arianne A. Zamora, Devon Ray Pacial, Juan Antonio R. Magalang, Marissa Alejandria, Celia Carlos, Anna Ong-Lim, Edsel Maurice Salvaña, John Q. Wong, Jaime C. Montoya, Maria Rosario Singh-Vergeire
Publication title: Microbiology Resource Announcements 10(18), May 2021

Abstract:
We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.
Full text link https://tinyurl.com/y9pmuyfu

Article title: Draft Genome Sequence of Multidrug-Resistant Vibrio parahaemolyticus Strain PH698, Infecting Penaeid Shrimp in the Philippines
Authors: Cynthia P. Saloma, Sarah Mae U. Penir, Joseph Matthew R. Azanza,aLeobert D. dela Pena, Roselyn C. Usero, Nikko Alvin R. Cabillon, Angela Denise P. Bilbao, Edgar C. Amar
Publication title: Microbiology Resource Announcements 8(47), November 2019

Abstract:
The emergence of multidrug-resistant bacterial strains in diverse settings has been reported globally. In the Philippine shrimp aquaculture industry, antibiotics are used for the treatment of bacterial diseases during the production cycle. We report the draft genome of Vibrio parahaemolyticus PH698, a multidrug-resistant strain isolated from a Philippine shrimp farm.
Full text link https://tinyurl.com/2nc3rb5v

Article title: The Green Revolution shaped the population structure of the rice pathogen Xanthomonas oryzae pv. oryzae
Authors: Ian Lorenzo Quibod, Genelou Atieza-Grande, Eula Gems Oreiro, Denice Palmos, Marian Hanna Nguyen, Sapphire Thea Coronejo, Ei Ei Aung, Cipto Nugroho, Veronica Roman-Reyna, Maria Ruby Burgos, Pauline Capistrano, Sylvestre G. Dossa, Geoffrey Onaga, Cynthia Saloma, Casiana Vera Cruz, Ricardo Oliva
Publication title: The ISME Journal 14(2), October 2019

Abstract:
The impact of modern agriculture on the evolutionary trajectory of plant pathogens is a central question for crop sustainability. The Green Revolution replaced traditional rice landraces with high-yielding varieties, creating a uniform selection pressure that allows measuring the effect of such intervention. In this study, we analyzed a unique historical pathogen record to assess the impact of a major resistance gene, Xa4, in the population structure of Xanthomonas oryzae pv. oryzae (Xoo) collected in the Philippines in a span of 40 years. After the deployment of Xa4 in the early 1960s, the emergence of virulent pathogen groups was associated with the increasing adoption of rice varieties carrying Xa4, which reached 80% of the total planted area. Whole genomes analysis of a representative sample suggested six major pathogen groups with distinctive signatures of selection in genes related to secretion system, cell-wall degradation, lipopolysaccharide production, and detoxification of host defense components. Association genetics also suggested that each population might evolve different mechanisms to adapt to Xa4. Interestingly, we found evidence of strong selective sweep affecting several populations in the mid-1980s, suggesting a major bottleneck that coincides with the peak of Xa4 deployment in the archipelago. Our study highlights how modern agricultural practices facilitate the adaptation of pathogens to overcome the effects of standard crop improvement efforts.
Full text link https://tinyurl.com/5n8kfxt2

Article title: Draft Genome Sequence of Vibrio parahaemolyticus Strain PH1339, Which Causes Acute Hepatopancreatic Necrosis Disease in Shrimp in the Philippines
Authors: Sarah Mae U. Penir, Leobert D. dela Pena, Nikko Alvin R. Cabillon, Angela Denise P. Bilbao, Edgar C. Amar, Cynthia P. Saloma
Publication title: Microbiology Resource Announcements 8(46), March 2019

Abstract:
We report the first draft genome sequence of an acute hepatopancreatic necrosis disease (AHPND)-causing Vibrio parahaemolyticus strain isolated from a Penaeus vannamei sample from the Philippines. The strain carries the genes encoding the Pir-like toxin pair PirA vp and PirB vp .
Full text link https://tinyurl.com/yckmf6s2

Article title: Genome-wide Analysis for Variants in Philippine Trypanosoma evansi Isolates with Varying Drug Resistance Profiles
Authors: Jose Enrico H. Lazaro, Neil Andrew D. Bascos, Francis A. Tablizo, Nancy S. Abes, Renlyn Ivy DG. Paynaganan, Michelle A. Miguel, Hector M. Espiritu, Mary Rose D. Uy, Claro N. Mingala, and Cynthia P. Saloma
Publication title: Philippine Journal of Science148 (S1): 219-233, Special Issue on Genomics, March 2019

Abstract:
Surra, a parasitic disease transmitted by hematophagous flies and caused by Trypanosoma evansi, affects many domesticated animals-including water buffaloes, camels, horses, pigs, dogs, and other carnivores-throughout the world. When left untreated, this disease can cause anemia, significant loss of weight, abortion, and death in affected animals. Among Philippine isolates of T. evansi, variability has been reported in terms of virulence as well as response to drug treatment. In this study, trypanosoma-positive blood was obtained from 15 Philippine water buffalo samples from different sites in the country. The collected T. evansi strains were propagated in mice then subjected to in vivo virulence, in vitro drug sensitivity testing, and whole genome sequencing. One strain (O14) was found to be highly virulent in vivo, and was found to be resistant to three commonly used drugs [i.e., isometamidium chloride (IC), diminazene diaceturate (DD), and melarsamine hydrochloride (CY for Cymelarsan®)] in vitro. This highly resistant sample was compared with two less-virulent strains using genome-wide analysis of single nucleotide polymorphisms (SNPs) and short insertions and deletions (indels) relative to the reference strain STIB 805. Variant analysis between O14 and the less virulent strains (M4 and C117) identified a number of distinctive SNPs, many of which corroborate previous data. Genes with relatively high copy numbers were observed in mutation hotspots. These included genes that code for variant surface glycoproteins (VSGs), expression site-associated genes (ESAGs), retrotransposon hot spot (RHS) proteins, and leucine rich repeat proteins. Notable mutations were also predicted from genes coding for membrane transporters and cysteine peptidases, as well as those involved in RNA degradation. The whole genome sequences acquired from the Philippine isolates (O14, M4, and C117) vary greatly from the reference strain (STIB 805). These WGS data serve as a good resource for the discovery of genetic and phenotypic features that may be translated to effective treatment strategies, relevant to the Philippine setting
Full text link https://tinyurl.com/shfu8zjy

Article title: Differential Expression Analysis in High-yielding and Low-yielding Philippine Coconut through Transcriptome Sequencing
Authors: Ma. Regina Punzalan, Gamaliel Lysander Cabria, Ma. Anita Bautista, Ernesto Emmanuel, Ramon Rivera, Susan Rivera, and Cynthia Saloma
Publication title: Philippine Journal of Science 148(S1):83-95, March 2019

Abstract:
The demand for coconut oil (CNO) continues to rise in the global market. This puts pressure for coconut-producing countries such as the Philippines to increase CNO and copra production. Baybay Tall (BAYT) is known to have the highest copra yield among the tall coconut varieties in the Philippines. However, traditional breeding techniques that rely on the use of morphological markers are very limited, laborious, and time-consuming. In order to improve breeding strategies for increased copra production, differential gene expression analysis was performed on coconut shell and kernel of high-yielding and low-yielding palms. High-quality RNA was isolated from the endosperm (ES or kernel) and endocarp (EC or shell) of nut tissues followed by transcriptome sequencing using Illumina HiSeq2000. De novo transcriptome assembly was performed using Trinity. Read abundance was estimated using Corset and differentially expressed genes were identified using edgeR. In total, 1,945 genes were found to be differentially expressed (FDR < 0.05) from the nut tissues. Annotation of the transcripts revealed that only 82 of the differentially expressed genes have significant annotation. Potential gene-targeted markers (GTMs) were designed for 64 candidate genes, which can be further validated for possible use in the marker-assisted selection of high-yielding palms. Microsatellite (SSR) sequences were identified in 19,147 unigenes in the EC and 17,394 in the ES. However, only two SSRs were found among differentially expressed genes in the EC and only one in the ES. Functional analysis revealed that high nut yield could arise from concerted actions of several transcription activators and regulatory proteins leading to increased cell division, secondary cell wall formation, enhanced energy metabolism, and activated stress response. Taken together, these processes contribute to increased kernel volume and thus increase in copra yield. Identified genes in this study can be used as potential targets in improving productivity in the Philippine coconut.
Full text link https://tinyurl.com/yckb6suy

Article title: Non-additive effects of ACVR2A in preeclampsia in a Philippine population
Authors: Melissa D. Amosco1,2*†, Gloria R. Tavera3†, Van Anthony M. Villar4, Justin Michael A. Naniong1,Lara Marie G. David-Bustamante2, Scott M. Williams3, Pedro A. Jose4,5and Cynthia P. Palmes-Saloma
Publication title: BMC Pregnancy and Childbirth 19(1), January 2019

Abstract:
Background: Multiple interrelated pathways contribute to the pathogenesis of preeclampsia, and variants in susceptibility genes may play a role among Filipinos, an ethnically distinct group with high prevalence of the disease. The objective of this study was to examine the association between variants in maternal candidate genes and the development of preeclampsia in a Philippine population.

Methods: A case-control study involving 29 single nucleotide polymorphisms (SNPs) in 21 candidate genes was conducted in 150 patients with preeclampsia (cases) and 175 women with uncomplicated normal pregnancies (controls). Genotyping for the GRK4 and DRD1 gene variants was carried out using the TaqMan Assay, and all other variants were assayed using the Sequenom MassARRAY Iplex Platform. PLINK was used for SNP association testing. Multilocus association analysis was performed using multifactor dimensionality reduction (MDR) analysis.

Results: Among the clinical factors, older age (P < 1 × 10–4), higher BMI (P < 1 × 10–4), having a new partner (P = 0.006), and increased time interval from previous pregnancy (P = 0.018) associated with preeclampsia. The MDR algorithm identified the genetic variant ACVR2A rs1014064 as interacting with age and BMI in association with preeclampsia among Filipino women.

Conclusions: The MDR algorithm identified an interaction between age, BMI and ACVR2A rs1014064, indicating that context among genetic variants and demographic/clinical factors may be crucial to understanding the pathogenesis of preeclampsia among Filipino women. Electronic supplementary material The online version of this article (10.1186/s12884-018-2152-z) contains supplementary material, which is available to authorized users.
Full text link https://tinyurl.com/5y4435s9

Article title: Biophysical and Functional Characterization of asFP504, a Novel Fluorescent Protein from the Philippines
Authors: Neil Andrew David Bascos, Francine Lianne C. Emralino, Franco Carlos Liu, Carla P. Concepcion, Marvin Altamia, Yen-Chieh Huang, Yin-Cheng Hsieh, Chun-Jung Chen, and Cynthia Palmes-Saloma
Publication title: Philippine Journal of Science 147(1):65-74, March 2018

Abstract:
Fluorescent proteins have proven to be invaluable for a myriad of applications in scientific research. The discovery and characterization of novel fluorescent proteins promises to expand this range even further. This report focuses on the biophysical and functional characterization of a novel green fluorescent protein cloned from a Philippine soft coral species. The asFP504 protein showed peak excitation at 471 nm and at 494 nm (λ E1 = 471 nm; λ E2 =494 nm), its emission maximum from 471 nm excitation was observed at 504 nm. The fluorescence was observed to be related to its oligomeric state. Both fluorescence and oligomerization were robustly maintained for a range of temperatures, pH conditions, treatment with chaotropic agents, and proteolysis. X-ray crystallography documented a molecular packing of three dimers within each asymmetric unit for the asFP504 protein. The observed absorbance and fluorescence properties are comparable to that of commercially available fluorescence proteins. Despite its lower absorbance, asFP504 has higher quantum yield than mCitrine. In addition, the stability of asFP504 in the presence of multiple denaturants presents the potential of this protein-the first fluorescent protein from the Philippines-for use in many different research applications.
Full text link https://tinyurl.com/yc65n7wd

Article title: Mortality of Pond-cultured Litopenaeus vannamei Associated with Acute Hepatopancreatic Necrosis Disease (AHPND) and White Spot Syndrome Virus (WSSV) Infection in the Philippines
Authors: Leobert D. de la Peña, Nikko Alvin R. Cabillon, Edgar C. Amar, Demy D. Catedral, Roselyn C. Usero, Joseph P. Faisan, Jr., Joey I. Arboleda, Wilberto D. Monotilla, Adelaida T. Calpe, Dalisay D. G. Fernandez and Cynthia P. Saloma
Publication title: Fish Pathology 52(1):38-41, April 2017

Abstract:
Mortalities of up to 60% were observed in pond-cultured Litopenaeus vannamei in Bohol, Philippines. Histopathological examination revealed typical acute hepatopancreatic necrosis disease (AHPND) pathology. PCR test generated 1,269 bp and 230 bp amplicons confirmative for the toxin-producing AHPND strain of Vibrio parahaemolyticus among shrimp sampled from eight ponds. The same samples were subjected to PCR analyses for the presence of other viruses, namely WSSV, IHHNV, IMNV, and TSV. The samples were negative for the viruses except WSSV, which was detected after one-step PCR in six out of eight ponds. These results suggested that shrimp were infected dually with AHPND V. parahaemolyticus and WSSV.
Full text link https://tinyurl.com/44y5cthe

Article title: VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population
Authors: Melissa D. Amosco, Van Anthony M. Villar, Justin Michael A. Naniong, LaraMarie G. David-Bustamante, Pedro A. Jose & Cynthia P. Palmes-Saloma
Publication title: Clinical and Experimental Hypertension 38(7):1-8, September 2016

Abstract:
The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

Full text link https://tinyurl.com/22e4nc4c

Article title: Targeted Next Generation Sequencing of the Entire Vitamin D Receptor Gene Reveals Polymorphisms Correlated with Vitamin D Deficiency among Older Filipino Women With and Without Fragility Fracture
Authors: Mark Pretzel Zumaraga, Paul Julius Medina, Juan Miguel Recto, Lauro Abrahan, Edelyn Azurin, Celeste C. Tanchoco, Cecilia A. Jimeno, Cynthia Palmes-Saloma
Publication title: The Journal of Nutritional Biochemistry 41, December 2016

Abstract:
This study aimed to discover genetic variants in the entire 101 kB vitamin D receptor (VDR) gene for vitamin D deficiency in a group of post-menopausal Filipino women using targeted next generation sequencing (TNGS) approach in a case–control study design. A total of fifty women with and without osteoporotic fracture seen at the Philippine Orthopedic Center were included. Blood samples were collected for determination of serum vitamin D, calcium, phosphorus, glucose, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase and as primary source for targeted VDR gene sequencing using the Ion Torrent Personal Genome Machine. The variant calling was based on the GATK best practice workflow and annotated using Annovar tool. A total of 1496 unique variants in the whole 101 kb VDR gene were identified. Novel sequence variations not registered in the dbSNP database were found among cases and controls at a rate of 23.1% and 16.6% of total discovered variants, respectively. One disease-associated enhancer showed statistically significant association to low serum 25-hydroxy vitamin D levels (Pearson chi square p-value=0.009). The transcription factor binding site prediction program PROMO predicted the disruption of three transcription factor binding sites in this enhancer region. These findings show the power of TNGS in identifying sequence variations in a very large gene and the surprising results obtained in this study greatly expand the catalogue of known VDR sequence variants that may represent an important clue in the emergence of vitamin D deficiency. Such information will also provide the additional guidance toward a personalized nutritional advice to reach a sufficient vitamin D status.
Full text available upon request to the author

Article title: Acute hepatopancreatic necrosis disease (AHPND) outbreaks in Penaeus vannamei and P. monodon cultured in the Philippines
Authors: Leobert D. de la Peña, Nikko Alvin R. Cabillon, Demy D. Catedral, Edgar C. Amar, Roselyn C. Usero, Wilberto D. Monotilla, Adelaida T. Calpe,Dalisay DG. Fernandez, Cynthia P. Saloma
Publication title: Diseases of Aquatic Organisms 116(3), October 2015

Abstract:
Acute hepatopancreatic necrosis disease (AHPND) has recently emerged as a serious disease of cultured shrimp. It has also been described as early mortality syndrome (EMS) due to mass mortalities occurring within 20 to 30 d after stocking of ponds with postlarvae. Here, Penaeus vannamei and Penaeus monodon from shrimp farms in the Philippines were examined for the toxin-producing strain of Vibrio parahaemolyticus due to AHPND-like symptoms occurring in marketable size shrimp. In the P. vannamei, histology revealed typical AHPND pathology, such as sloughing of undifferentiated cells in the hepatopancreatic tubule epithelium. Analysis using the IQ2000 AHPND/EMS Toxin 1 PCR test generated 218 bp and 432 bp amplicons confirmative of the toxin-producing strain of V. parahaemolyticus among shrimp sampled from 8 of 9 ponds. In the P. monodon, histology revealed massive sloughing of undifferentiated cells of the hepatopancreatic tubule epithelium in the absence of basophilic bacterial cells. PCR testing generated the 2 amplicons confirmatory for AHPND among shrimp sampled from 5 of 7 ponds. This study confirms the presence of AHPND in P. vannamei and P. monodon farmed in the Philippines and suggests that the disease can also impact late-stage juvenile shrimp.
Full text link https://tinyurl.com/4utthhsk

Article title: Prior Individual Training and Self-Organized Queuing during Group Emergency Escape of Mice from Water Pool
Authors: Caesar Saloma, Gay Jane Perez, Catherine Ann Gavile,Jacqueline Judith Ick-Joson, Cynthia Palmes-Saloma
Publication title: PLoS ONE 10(2):e0118508, February 2015

Abstract:
We study the impact of prior individual training during group emergency evacuation using mice that escape from an enclosed water pool to a dry platform via any of two possible exits. Experimenting with mice avoids serious ethical and legal issues that arise when dealing with unwitting human participants while minimizing concerns regarding the reliability of results obtained from simulated experiments using 'actors'. First, mice were trained separately and their individual escape times measured over several trials. Mice learned quickly to swim towards an exit-they achieved their fastest escape times within the first four trials. The trained mice were then placed together in the pool and allowed to escape. No two mice were permitted in the pool beforehand and only one could pass through an exit opening at any given time. At first trial, groups of trained mice escaped seven and five times faster than their corresponding control groups of untrained mice at pool occupancy rate ρ of 11.9% and 4%, respectively. Faster evacuation happened because trained mice: (a) had better recognition of the available pool space and took shorter escape routes to an exit, (b) were less likely to form arches that blocked an exit opening, and (c) utilized the two exits efficiently without preference. Trained groups achieved continuous egress without an apparent leader-coordinator (self-organized queuing)-a collective behavior not experienced during individual training. Queuing was unobserved in untrained groups where mice were prone to wall seeking, aimless swimming and/or blind copying that produced circuitous escape routes, biased exit use and clogging. The experiments also reveal that faster and less costly group training at ρ = 4%, yielded an average individual escape time that is comparable with individualized training. However, group training in a more crowded pool (ρ = 11.9%) produced a longer average individual escape time.
Full text link https://tinyurl.com/2p82f5xh

Article title: A bioinformatics survey for conotoxin-like sequences in three turrid snail venom duct transcriptomes
Authors: David Thomas T. Gonzales and Cynthia P. Saloma
Publication title: Toxicon 92, October 2014

Abstract:
The repertoire of venom peptides produced by Conoidean snails has shown to be useful for therapeutic and neuropharmacologic applications. Despite their dominance in terms of species number, the Family Turridae is the least studied among their other Conoidean counterparts. They provide a vast resource of pharmacological material only hindered by the inaccessibility of their deep water habitat for sample collection and their small size that allows only a limited amount of material from their venom duct amenable for analysis. Using high-throughput transcriptome sequencing, toxin transcripts can be extracted bioinformatically to fast-track toxin discovery. This approach was utilized on the venom duct transcriptomes of three species of turrids: Unedogemmula bisaya, Crassispira cerithina, and Gemmula speciosa and resulted in the discovery of 41, 22, and 74 putative turrid toxin genes, respectively. Comparisons among these turrid toxin genes to conotoxins show (i) similar superfamily precursors between conotoxins and turrid toxins for the classes D, I2, L, M, O1, O2, and P, (ii) a wider range of peptide lengths of up to 190 amino acids long for mature turritoxin, and (iii) nondisulfide-rich turritoxins with the B2 signal sequence. Novel superfamilies and cysteine frameworks including a novel 14-cysteine residue framework were also obtained.
Full text link https://tinyurl.com/2s9y3wj6

Article title: Superantigen involvement and susceptibility factors in Kawasaki disease: profiles of TCR Vβ2+ T cells and HLA-DRB1, TNF-α and ITPKC genes among Filipino patients
Authors: Magdalena F. Natividad, Celia Aurora T. Torres-Villanueva, Cynthia P. Saloma
Publication title: International Journal of Molecular Epidemiology and Genetics 4(1):70-6, April 2013

Abstract:
Superantigens and genetic factors may play roles in the etiology and susceptibility to Kawasaki disease (KD). To investigate these roles, percentages of TCR-Vβ2+ T cells were compared by flow cytometry using anti-Vβ2 monoclonal antibodies and genotyping was done on HLA-DRB1 exon 2, the -308 site of the TNF-α promoter region, and ITPKC SNP rs28493229 by polymerase chain reaction followed by direct sequencing. There were higher percentages of Vβ2+ T-cells in KD patients (9.5 ± 2.15%) compared to healthy controls (7.25 ± 1.48%) (P<0.05, Student's t-test, n=6-8/group). However, no polymorphisms were observed in exon 2 of HLA-DRB1 and in the -308 region of the TNF-α promoter. The ITPKC SNP rs28493229 G/C polymorphism was observed in 1 KD patient and 4 healthy controls. This study suggests that KD etiology may be associated with a superantigen and that HLA-DRB1 exon2, TNF-α -308 region and ITPKC SNP rs28493229 may not be associated with KD. This is the first study investigating Vβ2+ T cells and candidate genes involvement among Filipino KD patients.
Full text link https://tinyurl.com/y2hx3e82

Article title: Sorting Nexin 1 Loss Results in D-5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice
Authors: Van Anthony M. Villar, John Edward Jones, Ines Armando, Laureano D. Asico, Crisanto S. Escano, Jr., Hewang Lee, Xiaoyan Wang, Yu Yang, Annabelle M. Pascua-Crusan, Cynthia P. Palmes-Saloma,Robin A. Felder, and Pedro A. Jose
Publication title: Journal of Biological Chemistry 288(1), November 2012

Abstract:
The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D5R, and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D5R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor (AT1R) expression, of which expression was previously shown to be negatively regulated by D5R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D5R trafficking and that impairment of Snx1 expression or function results in D5R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension.
Full text link https://tinyurl.com/yck8f4us

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Dr. Cynthia P. Saloma