A5043403706- Glutathione Transferases and Polymorphisms
- Genomics, phytochemicals, and oxidative stress
- Insect Resistance and Genetics
- Pharmacogenetics and Drug Metabolism
- Mosquito-borne diseases and control
- Insect Pest Control Strategies
- Cholinesterase and Neurodegenerative Diseases
- Malaria Research and Control
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Viral Infections and Vectors
- Pesticide Exposure and Toxicity
- Insect symbiosis and bacterial influences
- Computational Drug Discovery Methods
- Folate and B Vitamins Research
- Viral Infections and Outbreaks Research
- Melanoma and MAPK Pathways
- Parasites and Host Interactions
- Drug-Induced Hepatotoxicity and Protection
- Insect and Pesticide Research
- Agriculture and Biological Studies
- Phytochemicals and Medicinal Plants
- Heat shock proteins research
- Cytokine Signaling Pathways and Interactions
- Nephrotoxicity and Medicinal Plants
Mahidol University
2014-2023
Imperial College London
1995-1997
University of London
1991-1996
London School of Hygiene & Tropical Medicine
1991-1996
Institute of Cancer Research
1996
The University of Queensland
1987-1989
Princess Alexandra Hospital
1987-1989
San Francisco General Hospital
1982-1987
University of California, San Francisco
1982-1987
University of California, Riverside
1978-1980
Anisomycin or osmotic stress induced by sorbitol activated c-Jun N-terminal protein kinases (JNKs) in ventricular myocytes cultured from neonatal rat hearts. After 15-30 min, JNK was 10-20-fold. Activation anisomycin transient, but that sustained for at least 4 h. In-gel assays confirmed activation of two renaturable JNKs 46 and 55 kDa (JNK-46 JNK-55, respectively). An antibody against human JNK1 immunoprecipitated JNK-46 activity. Endothelin-1, an activator extracellular signal-regulated...
In response to insulin-like growth factor-I (IGF-I), neonatal rat cardiac myocytes exhibit a hypertrophic response. The elucidation of the IGF-I signal transduction system in these cells remains unknown. We show here that present single class high affinity receptors (12,446 ± 3,669 binding sites/cell) with dissociation constant 0.36 0.10 nm. Two different β-subunits receptor were detected, and their autophosphorylation was followed by increases phosphotyrosine content extracellular...
The cytosolic GST (glutathione transferase) superfamily has been annotated in the Drosophila melanogaster genome database. Of 36 genes, four undergo alternative splicing to yield a total of 41 proteins. In present study, we have obtained transcripts encoding proteins by RT (reverse transcription)-PCR using RNA template from S2 cells, an embryonic cell line. This observation suggests that all DmGSTs (D. GSTs) proteome are expressed late stages D. melanogaster. To avoid confusion naming these...
The insect GST (glutathione transferase) supergene family encodes a varied group of proteins belonging to at least six individual classes. Interest in GSTs has focused on their role conferring insecticide resistance. Previously from the mosquito malaria vector Anopheles dirus, two genes encoding five Delta class have been characterized for structural as well enzyme activities. We obtained new gene and isoenzyme A. which we name adGSTD5-5. adGSTD5-5 was identified only detectably expressed...
Abstract Glutathione S‐transferases (GSTs) are dimeric proteins that play an important role in cellular detoxification. Four GSTs from the mosquito Anopheles dirus species B (Ad), malaria vector South East Asia, produced by alternate splicing of a single transcription product and were previously shown to have detoxifying activity towards pesticides such as DDT. We determined crystal structures for two these alternatively spliced proteins, AdGST1–3 (complexed with glutathione) AdGST1–4 (apo...
The enzyme, esterase B2, involved in insecticide resistance has been purified and characterized from the mosquito Culex quinquefasciatus. monomeric enzyme an M(r) of 62000 a pI 5.0. This is compared with A2 previously [Ketterman, Jayawardena Hemingway (1992) Biochem. J. 287, 355-360]. kinetic constants for interaction several insecticides indicate, as A2, that B2 role resistance. rates affinities binding observed support hypothesis mainly sequestration followed by slow turnover insecticide....
Parkinson's disease is the most frequent neurodegenerative motor disorder. The clinical syndrome and pathology involve disturbance degeneration of dopaminergic neurons in substantia nigra. Root extracts Withania. somnifera, commonly called Ashwagandha, contain several major chemical constituents known as withanolides. Studies have shown that W. somnifera exhibit numerous therapeutic effects including inflammation oxidative stress reduction, memory cognitive function improvement. This study...
Abstract DDT-resistant Anopheles gambiae Giles from Zanzibar, Tanzania, had increased levels of DDT-dehydrochlorination compared to a DDT-susceptible strain. Glutathione S-transferases (GSTs) are responsible for conversion DDT DDE in both the susceptible and resistant strains. Sequential column chromatography, including Q-Sepharose, S-hexylglutathione agarose, hydroxylapatite phenyl Sepharose, allowed partial purification seven GSTs. All GSTs possessed different degrees DDTase activity....
A carboxylesterase (EC 3.1.1.1) involved in organophosphate insecticide resistance has been purified and characterized from the mosquito Culex quinquefasciatus. The monomeric enzyme M(r) of 67,000 a pI 5.2. It hydrolysed medium-chain-length mono- di-acylglycerols addition to xenobiotic esters. Kinetic constants determined for four insecticides, temephos, chlorpyrifos, fenitrothion propoxur indicate rates acylation affinities binding insecticides this are important. This supports major role...
Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of is critical virus replication as only the activity used processing non-structural polypeptide. Chikungunya an emerging disease problem that becoming a world-wide health issue. We have generated purified recombinant chikungunya proteins, both full length truncated domain from C-terminus protein. Enzyme characterization shows alone has different properties compared with protease. also show...
Two malathion carboxylesterase fractions, designated as esterase fraction A and B, that hydrolyze were purified 13‐ 18‐fold, respectively, from rat liver microsomes. The two enzymes could not be distinguished kinetically, but contained at least one electrophoretic species present in B. molecular weight of was estimated 50,000–60,000; the B about twice this value. Incubation [methoxy‐ 14 C]malathion with or resulted a mixture β monoaclds, composition produced by (α/β = 1.5) differed 0.2),...
Glutathione transferases (GSTs) are protection enzymes capable of conjugating glutathione (GSH) to toxic compounds. During evolution an important catalytic cysteine residue involved in GSH activation was replaced by serine or, more recently, tyrosine. The utility these replacements represents enigma because they yield no improvements the affinity toward or its reactivity. Here we show that changes better protect cell from nitric oxide (NO) insults. In fact dinitrosyl·diglutathionyl·iron...
Structural investigations of a GST (glutathione transferase), adGSTD4-4, from the malaria vector Anopheles dirus show novel lock-and-key ‘Clasp’ motif in dimer interface Delta class enzyme. This also appears to be highly conserved across several insect classes, but differs previously reported mammalian motif. The aromatic ‘key’ residue not only inserts into hydrophobic pocket, ‘lock’, neighbouring subunit, acts as part ‘lock’ for other subunit ‘key’. residues both subunits ring stacking with...
Abstract Chikungunya virus is the pathogenic alphavirus that causes chikungunya fever in humans. In last decade millions of cases have been reported around world from Africa to Asia Americas. The nsP2 protein multifunctional and considered be pivotal viral replication, as protease activity critical for proteolytic processing polyprotein during replication. Classically thought papain-like with enzyme reaction proceeding through a cysteine/histidine catalytic dyad. We performed...