Displaying publications 1 - 20 of 74 in total

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  1. The anticoagulant activity of Malayan cobra (Naja naja sputatrix) venom and venom phospholipase A2 enzymes
    Tan NH, Arunmozhiarasi A
    Biochem. Int., 1989 Oct;19(4):803-10.
    PMID: 2619749
    Malayan cobra (Naja naja sputatrix) venom was found to exhibit an in vitro anticoagulant activity that was much stronger than most common cobra (genus Naja) venoms. The most potent anticoagulants of the venom are two lethal phospholipase A2 enzymes with pI's of 6.15 and 6.20, respectively. The anticoagulant activity of the venom is due to the synergistic effect of the venom phospholipase A2 enzymes and polypeptide anticoagulants. Bromophenacylation of the two phospholipase A2 enzymes reduced their enzymatic activity with a concomitant drop in both the lethal and anticoagulant activities.
    Matched MeSH terms: Phospholipases/pharmacology*; Phospholipases A/pharmacology*; Phospholipases A2
  2. Purification and characterization of two acidic phospholipase A2 enzymes from king cobra (Ophiophagus hannah) snake venom
    Tan NH, Saifuddin MN
    Int. J. Biochem., 1990;22(5):481-7.
    PMID: 2347427
    1. The two major phospholipase A2 enzymes (OHPLA-DE1 and OHPLA-DE2) of king cobra (Ophiophagus hannah) venom have been purified to electrophoretic homogeneity. 2. The isoelectric points of OHPLA-DE1 and OHPLA-DE2 were 3.81 and 3.89, respectively and the Mws were 14,000 and 15,000, respectively, as estimated by Sephadex G-75 gel filtration chromatography; and 14,000 as estimated by SDS-PAGE. 3. The enzymes were not lethal to mice at a dosage of 10 micrograms/g body wt by i.v. route. Both phospholipase A2 enzymes, however, exhibited moderate edema-inducing and anti-coagulant activities. 4. Bromophenacylation of the enzymes reduced the enzymatic activity drastically but did not affect the edema-inducing activity of the enzymes.
    Matched MeSH terms: Phospholipases/isolation & purification*; Phospholipases A/isolation & purification*; Phospholipases A/pharmacology; Phospholipases A/toxicity; Phospholipases A2
  3. Isolation and characterization of an acidic lethal phospholipase Az from Malayan cobra (Naja naja sputatrix) venom
    Tan NH, Arunmozhiarasi A
    Biochem. Int., 1989 Apr;18(4):785-92.
    PMID: 2764979
    An acidic, lethal phospholipase Az was purified to electrophoretic homogeneity from the venom of the Malayan cobra (Naja naja sputatrix). The enzyme has an isoelectric point of 5.58, a molecular weight of 12000, and a medium lethal dose (LD50) of 0.86 micrograms/g in mice by intravenous injection. The enzyme also exhibited weak anticoagulant and edema-forming activities. The amino acid composition of the enzyme is similar to those of other cobra venom phospholipases Az.
    Matched MeSH terms: Phospholipases/isolation & purification*; Phospholipases A/isolation & purification*; Phospholipases A/toxicity
  4. In vivo interactions between neurotoxin, cardiotoxin and phospholipases A2 isolated from Malayan cobra (Naja naja sputatrix) venom
    Tan NH, Armugam A
    Toxicon, 1990;28(10):1193-8.
    PMID: 2264068
    The in vivo interactions between alpha-neurotoxin, cardiotoxin and two phospholipases A2 (sputa-phospholipase A2-1 and 3) isolated from Malayan cobra venom were assessed by examining the effects of simultaneous injection of sub-LD50 dose of one toxin on (i) i.v. LD50 S of the other toxins in mice; and (ii) mean survival times of mice injected with lethal doses of the other toxins. While LD50 measurements did not reveal any interaction between the toxins in vivo, survival time measurements suggest a synergy between the neurotoxin and sputa-phospholipase A2-1 and between sputa-phospholipase A2-1 and sputa-phospholipase A2-3. Our results also suggest that both sputa-phospholipases A2 interfere with the lethal action of the cardiotoxin, resulting in prolongation of the mean survival time of mice injected with a lethal dose of cardiotoxin. The patterns of in vivo interactions between phospholipase A2 and other venom toxins appear to depend on the nature and mode of pharmacological action of the phospholipase A2.
    Matched MeSH terms: Phospholipases A/pharmacology*; Phospholipases A2
  5. The edema inducing activity of phospholipase A2 enzymes
    Tan NH, Saifuddin MN, Yong WY
    Biochem. Int., 1991 Jan;23(1):175-81.
    PMID: 1863271
    The edema inducing activity of phospholipase A2 (PLA2) enzymes from snake venoms and porcine pancreas was investigated using mouse paw as experimental model. All ten PLA2 enzymes exhibited potent edema inducing activity. PLA2, however, is generally not the major edema inducing component of snake venom. Chemical modification studies indicated that enzymatic activity of PLA2 was required for its edema inducing activity. All PLA2 enzymes examined displayed a rapid onset edema which was suppressed by pretreatment of the mice with antihistamine. Dexamethasone pretreatment also inhibited edemas elicited by some PLA2 enzymes.
    Matched MeSH terms: Phospholipases A/antagonists & inhibitors; Phospholipases A/metabolism; Phospholipases A/toxicity*; Phospholipases A/chemistry; Phospholipases A2
  6. Growth kinetics of Bacillus cytotoxicus in liquid Egg yolk during treatment with phospholipase A2 - A one-step global dynamic analysis
    Huang L, Ahmad NH, Juneja V, Stapp-Kamotani E, Gabiola J, Minocha U, et al.
    Food Microbiol, 2024 Apr;118:104420.
    PMID: 38049265 DOI: 10.1016/j.fm.2023.104420
    During commercial production of liquid egg yolk (LEY), phospholipase A2 (PLA2) is used to improve its emulsification capacity and thermal stability. The enzymatic treatment may occur at elevated temperatures such as 50 °C, potentially allowing foodborne pathogens, such as Bacillus cereus, to grow. Little knowledge is available concerning growth of B. cereus in LEY during PLA2 treatment. Therefore, the objective of this study was to investigate the growth kinetics of B. cereus during PLA2 treatment using pathogenic B. cytotoxicus NVH391-98, the most thermotolerant member in the B. cereus group, as a surrogate. Inoculated LEY samples were placed in precision programmable incubators to observe the growth of B. cytotoxicus NVH391-98 under multiple isothermal and dynamic temperature conditions between 20 and 53 °C. The bacterial growth was described using the differential Baranyi model coupled with two different secondary models. The kinetic parameters were determined using one-step dynamic inverse analysis of multiple growth curves. The least square method was used in combination with the 4th order Runge-Kutta method to solve the differential Baranyi model using multiple growth curves to determine the cardinal kinetic parameters. The results showed that B. cytotoxicus NVH391-98 can grow prolifically at 50 °C. The estimated minimum, optimum and maximum temperatures were 16.7 or 18.5, 47.8 or 48.1, and 52.1 or 52.4 °C, respectively, depending on the secondary models, with an optimum growth rate of 2.1 log colony-forming-unit (CFU)/g per hour. The dynamic model is validated using isothermal curves with reasonable accuracy. B. cytotoxicus died off slowly at 15 °C. At 55 °C, thermal inactivation was observed, with a D value of approximately 2.7 h. Holding at 55 °C or below 15 °C can effectively prevent the growth of B. cytotoxicus in egg yolk.
    Matched MeSH terms: Phospholipases; Phospholipases A2
  7. One-step analysis of growth kinetics of mesophilic Bacillus cereus in liquid egg yolk during treatment with phospholipase A2: Model development and validation
    Ahmad NH, Huang L, Juneja V
    Food Res Int, 2024 Jan;176:113786.
    PMID: 38163703 DOI: 10.1016/j.foodres.2023.113786
    Liquid egg yolk (LEY) is often treated with phospholipase A2 (PLA2) to improve its emulsifying capacity and thermal stability. However, this process may allow certain pathogens to grow. The objective of this study was to evaluate the growth kinetics of mesophilic Bacillus cereus in LEY during PLA2 treatment. Samples, inoculated with B. cereus vegetative cells, were incubated isothermally at different temperatures between 9 and 50 °C to observe the bacterial growth and survival. Under the observation conditions, bacterial growth occurred between 15 and 48 °C, but not at 9 and 50 °C. The growth curves were analyzed using the USDA IPMP-Global Fit, with the no-lag phase model as the primary model in combination with either the cardinal temperatures model (CTM) or the Huang square-root model (HSRM) as the secondary model. While similar maximum growth temperatures (Tmax) were determined (48.4 °C for HSRM and 48.1 °C for CTM), the minimum growth temperature (Tmin) of the HSRM more accurately described the lower limit (9.26 °C), in contrast to 6.51 °C for CTM, suggesting that the combination of the no-lag phase model and HSRM was more suitable to describe the growth of mesophilic B. cereus in LEY. The root mean square error (RMSE) of model validation and development was <0.5 log CFU/g, indicating the combination of the no-lag phase model and HSRM could predict the growth of mesophilic B. cereus in LEY during PLA2 treatment. The results of this study may allow the food industry to choose a suitable temperature for PLA2 treatment of LEY to prevent the growth of mesophilic B. cereus.
    Matched MeSH terms: Phospholipases; Phospholipases A2
  8. Acidimetric assay for phospholipase A using egg yolk suspension as substrate
    Tan NH, Tan CS
    Anal Biochem, 1988 May 1;170(2):282-8.
    PMID: 3394929
    A convenient acidimetric assay for phospholipase A using egg yolk suspension as substrate has been developed. The substrate mixture consists of 1 part egg yolk, 1 part 8.1 mM sodium deoxycholate, and 1 part 18 mM calcium chloride. Phospholipase A activity is measured by following the initial rate of pH change, which is linear between pH 8.0 and 7.75 and is proportional to enzyme concentration over a wide range. The assay is highly reproducible, with a coefficient of variation of 3%, and as sensitive as most established assays for phospholipase A. The assay uses inexpensive and easily available substrate and is simple to perform. It is particularly useful for monitoring phospholipase A activity in chromatography fractions.
    Matched MeSH terms: Phospholipases/analysis*; Phospholipases A/analysis*
  9. Isolation and characterization of the major phospholipase A2 from the venom of Trimeresurus purpureomaculatus (shore pit viper)
    Nget Hong Tan, Chon Seng Tan, Hun Teck Khor
    Int. J. Biochem., 1989;21(12):1421-6.
    PMID: 2612728
    1. The major phospholipase A2 (PLA-DE4) of the venom of Trimeresurus purpureomaculatus (shore pit viper) has been purified to electrophoretic homogeneity. 2. The isoelectric point of the purified enzyme was determined to be 4.20, and the mol. wt was 31,700 as estimated by Sephadex G-75 gel filtration chromatography; and 14,000 as estimated by SDS-polyacrylamide gel electrophoresis. The purified enzyme hydrolyzed phosphatidylcholine (PC) faster than phosphatidylethanolamine (PE), whereas phosphatidylserine (PS) was not hydrolyzed at all (PC greater than PE greater than PS =0). However, in reaction system consisted of mixtures of PC and PS, phosphatidylserine was effectively hydrolyzed by the enzyme. 4. The phospholipase A2 exhibited edema-forming activity but not hemolytic, hemorrhagic or anticoagulant activities. It was not lethal to mice at a dosage of 10 micrograms/g by i.v. route.
    Matched MeSH terms: Phospholipases/isolation & purification*; Phospholipases A/isolation & purification*; Phospholipases A/metabolism; Phospholipases A/toxicity; Phospholipases A2
  10. Fulltext Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase
    Hiu JJ, Yap MKK
    Biochem Soc Trans, 2020 04 29;48(2):719-731.
    PMID: 32267491 DOI: 10.1042/BST20200110
    The phospholipase A2 (PLA2) and l-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA2 and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA2 to produce reactive oxygen species during lipolysis and formation of H2O2 from LAAO catalytic activity which consequently lead to cell death. Nonetheless, the cell-death signalling pathways associated with exposure to these enzymatic toxins are not fully elucidated yet. Here in this review, we will discuss the cytotoxic effects of PLA2 and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.
    Matched MeSH terms: Phospholipases A2; Phospholipases A2, Cytosolic
  11. Fulltext The role of group IIA secretory phospholipase A2 (sPLA2-IIA) as a biomarker for the diagnosis of sepsis and bacterial infection in adults-A systematic review
    Tan TL, Goh YY
    PLoS One, 2017;12(7):e0180554.
    PMID: 28671974 DOI: 10.1371/journal.pone.0180554
    INTRODUCTION: This paper investigates the role of Group II Secretory Phospholipase A2 (sPLA2-IIA) as a biomarker for the diagnosis of sepsis and bacterial infection in adults. Sepsis and bacterial infection are common problems encountered by patients in the hospital and often carry adverse outcomes if not managed early.

    METHODS: Two independent reviewers conducted a comprehensive search using Ovid MEDLINE published from years 1993 to 2016 and SCOPUS published from year 1985 to 2017 to screen for relevant studies. The main inclusion criteria included adult subjects, patients with suspected or confirmed signs of infection and relevant outcomes which looked into the role of sPLA2-IIA in detecting the presence of sepsis and bacterial infection in the subjects.

    RESULTS AND DISCUSSION: Four studies met the inclusion criteria. SPLA2-IIA was found to be effective in detecting the presence of sepsis and bacterial infection in adults. The levels of serum sPLA2-IIA also correlated well with the presence of sepsis and bacterial infection.

    CONCLUSION: This systematic review highlights the role of sPLA2-IIA as a reliable tool to diagnose sepsis and bacterial infection in adult patients. Nonetheless, further studies should be done in the future to provide more compelling evidence on its application in the clinical setting.

    Matched MeSH terms: Group II Phospholipases A2/blood*
  12. Haemolytic and phospholipase A activities of the tentacle extract of Catostylus mosaicus
    Azila N, Othman I
    Biochem. Int., 1990;20(2):291-9.
    PMID: 1969267
    An extract prepared from the tentacle of Catostylus mosaicus was shown to lyse erythrocytes from rat, rabbit and human to a different extent; those from the rat being most susceptible followed by those from rabbit and human. The haemolytic activity was dependent on the concentration of crude extract protein exhibiting a sigmoidal curve. Only 60% of the haemolytic activity was retained after treament with heat and proteolytic enzyme. The extract was devoid of hydrolytic enzymes normally present in venoms except for phospholipase A activity, which resulted in the hydrolysis of membrane phospholipids with concomittant appearance of their lyso-derivatives.
    Matched MeSH terms: Phospholipases/metabolism*; Phospholipases A/metabolism*
  13. Regional and accelerated molecular evolution in group I snake venom gland phospholipase A2 isozymes
    Chuman Y, Nobuhisa I, Ogawa T, Deshimaru M, Chijiwa T, Tan NH, et al.
    Toxicon, 2000 Mar;38(3):449-62.
    PMID: 10669032
    In accordance with detection of a few phospholipase A2 (PLA2) isozyme genes by Southern blot analysis, only two cDNAs, named NnkPLA-I , and NnkPLA-II, encoding group I PLA2s, NnkPLA-I and NnkPLA-II, respectively, were isolated from the venom gland cDNA library of Elapinae Naja naja kaouthia of Malaysia. NnkPLA-I and NnkPLA-II showed four amino acid substitutions, all of which were brought about by single nucleotide substitution. No existence of clones encoding CM-II and CM-III, PLA2 isozymes which had been isolated from the venom of N. naja kaouthia of Thailand, in Malaysian N. naja kaouthia venom gland cDNA library was verified by dot blot hybridization analysis with particular probes. NnkPLA-I and NnkPLA-II differed from CM-II and CM-III with four and two amino acid substitutions, respectively, suggesting that their molecular evolution is regional. The comparison of NnkPLA-I, NnkPLA-II and cDNAs encoding other group I snake venom gland PLA2s indicated that the 5'- and 3'-untranslated regions are more conserved than the mature protein-coding region and that the number of nucleotide substitutions per nonsynonymous site is almost equal to that per synonymous site in the protein-coding region, suggesting that accelerated evolution has occurred in group I venom gland PLA2s possibly to acquire new physiological functions.
    Matched MeSH terms: Phospholipases A/genetics; Phospholipases A/chemistry*; Phospholipases A2
  14. An investigation into the antigenic cross-reactivity of Ophiophagus hannah (king cobra) venom neurotoxin, phospholipase A2, hemorrhagin and L-amino acid oxidase using enzyme-linked immunosorbent assay
    Tan NH, Lim KK, Jaafar MI
    Toxicon, 1993 Jul;31(7):865-72.
    PMID: 8212031
    The antigenic cross-reactivity of four Ophiophagus hannah (king cobra) venom components, the neurotoxin (OH-NTX), phospholipase A2 (OH-PLA2), hemorrhagin (OH-HMG) and L-amino acid oxidase (OH-LAAO) were examined by indirect and double sandwich ELISAs. The indirect ELISAs for OH-NTX, OH-PLA2 and OH-HMG were very specific when assayed against the various heterologous snake venoms and O. hannah venom components, at 25 ng/ml antigen level. At higher antigen concentrations (100-400 ng/ml), there were moderate to strong indirect ELISA cross-reactions between anti-O. hannah neurotoxin and venoms from various species of cobra as well as two short neurotoxins. However, anti-O. hannah hemorrhagin did not cross-react with any of the venoms tested, even at these high antigen concentrations, indicating that O. hannah hemorrhagin is antigenically very different from other venom hemorrhagins. Examination of the indirect ELISA cross-reactions between anti-O. hannah PLA2 and several elapid PLA2 enzymes suggests that the elapid PLA2 antigenic class has more than two subgroups. The antibodies to O. hannah L-amino acid oxidase, however, yielded indirect ELISA cross-reactions with many venoms as well as with OH-NTX, OH-PLA2 and OH-HMG, indicating that OH-LAAO shares common epitopes even with unrelated proteins. The double sandwich ELISAs for the four anti-O. hannah venom components, on the other hand, generally exhibited a higher degree of selectivity than the indirect ELISA procedure.
    Matched MeSH terms: Phospholipases A/immunology*; Phospholipases A2
  15. Fulltext Venom proteomics and antivenom neutralization for the Chinese eastern Russell's viper, Daboia siamensis from Guangxi and Taiwan
    Tan KY, Tan NH, Tan CH
    Sci Rep, 2018 06 04;8(1):8545.
    PMID: 29867131 DOI: 10.1038/s41598-018-25955-y
    The eastern Russell's viper (Daboia siamensis) causes primarily hemotoxic envenomation. Applying shotgun proteomic approach, the present study unveiled the protein complexity and geographical variation of eastern D. siamensis venoms originated from Guangxi and Taiwan. The snake venoms from the two geographical locales shared comparable expression of major proteins notwithstanding variability in their toxin proteoforms. More than 90% of total venom proteins belong to the toxin families of Kunitz-type serine protease inhibitor, phospholipase A2, C-type lectin/lectin-like protein, serine protease and metalloproteinase. Daboia siamensis Monovalent Antivenom produced in Taiwan (DsMAV-Taiwan) was immunoreactive toward the Guangxi D. siamensis venom, and effectively neutralized the venom lethality at a potency of 1.41 mg venom per ml antivenom. This was corroborated by the antivenom effective neutralization against the venom procoagulant (ED = 0.044 ± 0.002 µl, 2.03 ± 0.12 mg/ml) and hemorrhagic (ED50 = 0.871 ± 0.159 µl, 7.85 ± 3.70 mg/ml) effects. The hetero-specific Chinese pit viper antivenoms i.e. Deinagkistrodon acutus Monovalent Antivenom and Gloydius brevicaudus Monovalent Antivenom showed negligible immunoreactivity and poor neutralization against the Guangxi D. siamensis venom. The findings suggest the need for improving treatment of D. siamensis envenomation in the region through the production and the use of appropriate antivenom.
    Matched MeSH terms: Phospholipases A2/immunology; Phospholipases A2/toxicity
  16. Unlocking the secrets of banded coral snake (Calliophis intestinalis, Malaysia): A venom with proteome novelty, low toxicity and distinct antigenicity
    Tan KY, Liew JL, Tan NH, Quah ESH, Ismail AK, Tan CH
    J Proteomics, 2019 02 10;192:246-257.
    PMID: 30243938 DOI: 10.1016/j.jprot.2018.09.006
    The Asiatic coral snakes are basal in the phylogeny of coral snakes. Although envenoming by the Asiatic coral snakes is rarely fatal, little is known about their venom properties and variability from the American coral snakes. Integrating reverse-phase high performance liquid chromatography and nano-liquid chromatography-tandem mass spectrometry, we showed that the venom proteome of the Malaysian banded or striped coral snake (Calliophis intestinalis) was composed of mainly phospholipases A2 (PLA2, 43.4%) and three-finger toxins (3FTx, 20.1%). Within 3FTx, the cytotoxins or cardiotoxins (CTX) dominated while the neurotoxins' content was much lower. Its subproteomic details contrasted with the 3FTx profile of most Micrurus sp., illustrating a unique dichotomy of venom phenotype between the Old and the New World coral snakes. Calliophis intestinalis venom proteome was correlated with measured enzymatic activities, and in vivo it was myotoxic but non-lethal to mice, frogs and geckos at high doses (5-10 μg/g). The venom contains species-specific toxins with distinct sequences and antigenicity, and the antibodies raised against PLA2 and CTX of other elapids showed poor binding toward its venom antigens. The unique venom proteome of C. intestinalis unveiled a repertoire of novel toxins, and the toxicity test supported the need for post-bite monitoring of myotoxic complication. SIGNIFICANCE: Malaysian banded or striped coral snake (Calliophis intestinalis) has a cytotoxin (CTX)-predominating venom proteome, a characteristic shared by its congener, the Malayan blue coral snake (Calliophis bivirgata). With little neurotoxins (NTX), it illustrates a CTX/NTX dichotomy of venom phenotype between the Old World and the New World coral snakes. The low toxicity of the venom imply that C. intestinalis bite envenoming can be managed via symptomatic relief of the mild to moderate pain with appropriate analgesia. Systemically, the serum creatine kinase level of patients should be monitored serially for potential complication of myotoxicity. The distinct antigenicity of the venom proteins implies that the empirical use of heterologous antivenom is mostly inappropriate and not recommended.
    Matched MeSH terms: Phospholipases A2/genetics; Phospholipases A2/metabolism*
  17. Cloning and characterization of cDNAs encoding three isoforms of phospholipase A2 in Malayan spitting cobra (Naja naja sputatrix) venom
    Armugam A, Earnest L, Chung MC, Gopalakrishnakone P, Tan CH, Tan NH, et al.
    Toxicon, 1997 Jan;35(1):27-37.
    PMID: 9028006
    cDNAs encoding three phospholipase A2 (PLA2) isoforms in Naja naja sputatrix were cloned and characterized. One of them encoded an acidic PLA2 (APLA) while the others encoded neutral PLA2 (NPLA-1 and NPLA-2). The specific characteristics of APLA and NPLA were attributed to mutations at nt139 and nt328 from G to C and G to A, respectively, resulting in amino acid substitutions from Asp20 and 83 in APLA to His20 and Asn83 in NPLA. Amino acid sequencing of purified protein also showed the presence of this Asp20 and His20 in APLA and NPLA, respectively. The cDNA encoding one of the PLA2 (NAJPLA-2A), when expressed in Escherichia coli, yielded a protein that exhibited PLA2 activity.
    Matched MeSH terms: Phospholipases A/genetics*; Phospholipases A/isolation & purification; Phospholipases A/chemistry*; Phospholipases A2
  18. Differential expression and geographic variation of the venom phospholipases A2 of Calloselasma rhodostoma and Trimeresurus mucrosquamatus
    Tsai IH, Chen YH, Wang YM, Liau MY, Lu PJ
    Arch Biochem Biophys, 2001 Mar 15;387(2):257-64.
    PMID: 11370849
    To investigate the geographic variations in venoms of two medically important pitvipers, we have purified and characterized the phospholipases A2 (PLA2s) from the pooled venoms of Calloselasma rhodostoma from Malaysia, Thailand, Indonesia, and Vietnam, as well as the individual venom of Trimeresurus mucrosquamatus collected from both North and South Taiwan. Enzymatic and pharmacological activities of the purified PLA2s were also investigated. The complete amino acid sequences of the purified PLA2s were determined by sequencing the corresponding cDNAs from the venom gland and shown to be consistent with their molecular weight data and the N-terminal sequences. All the geographic venom samples of C. rhodostoma contain a major noncatalytic basic PLA2-homolog and two or three acidic PLA2s in different proportions. These acidic PLA2s contain Glu6-substitutions and show distinct inhibiting specificities toward the platelets from human and rabbit. We also found that the T. mucrosquamatus venoms from North Taiwan but not those from South Taiwan contain an Arg6-PLA2 designated as TmPL-III. Its amino acid sequence is reported for the first time. This enzyme is structurally almost identical to the low- or nonexpressed Arg6-PLA2 from C. rhodostoma venom gland, and thus appears to be a regressing venom component in both of the Asian pitvipers.
    Matched MeSH terms: Phospholipases A/genetics*; Phospholipases A/pharmacology; Phospholipases A/chemistry; Phospholipases A2; Group II Phospholipases A2
  19. Fulltext In Silico and In Vitro Study of the Bromelain-Phytochemical Complex Inhibition of Phospholipase A2 (Pla2)
    Mohamed Tap F, Abd Majid FA, Ismail HF, Wong TS, Shameli K, Miyake M, et al.
    Molecules, 2018 Jan 19;23(1).
    PMID: 29351216 DOI: 10.3390/molecules23010073
    Phospholipase A2 (Pla2) is an enzyme that induces inflammation, making Pla2 activity an effective approach to reduce inflammation. Therefore, investigating natural compounds for this Pla2 inhibitory activity has important therapeutic potential. The objective of this study was to investigate the potential in bromelain-phytochemical complex inhibitors via a combination of in silico and in vitro methods. Bromelain-amenthoflavone displays antagonistic effects on Pla2. Bromelian-asiaticoside and bromelain-diosgenin displayed synergistic effects at high concentrations of the combined compounds, with inhibition percentages of more than 70% and 90%, respectively, and antagonistic effects at low concentrations. The synergistic effect of the bromelain-asiaticoside and bromelain-diosgenin combinations represents a new application in treating inflammation. These findings not only provide significant quantitative data, but also provide an insight on valuable implications for the combined use of bromelain with asiaticoside and diosgenin in treating inflammation, and may help researchers develop more natural bioactive compounds in daily foods as anti-inflammatory agent.
    Matched MeSH terms: Phospholipases A2/metabolism*; Phospholipases A2/chemistry*
  20. Fulltext New quinoxalinone inhibitors targeting secreted phospholipase A2 and α-glucosidase
    Alasmary FAS, Alnahdi FS, Ben Bacha A, El-Araby AM, Moubayed N, Alafeefy AM, et al.
    J Enzyme Inhib Med Chem, 2017 Dec;32(1):1143-1151.
    PMID: 28856929 DOI: 10.1080/14756366.2017.1363743
    Elevated blood glucose and increased activities of secreted phospholipase A2 (sPLA2) are strongly linked to coronary heart disease. In this report, our goal was to develop small heterocyclic compound that inhibit sPLA2. The title compounds were also tested against α-glucosidase and α-amylase. This array of enzymes was selected due to their implication in blood glucose regulation and diabetic cardiovascular complications. Therefore, two distinct series of quinoxalinone derivatives were synthesised; 3-[N'-(substituted-benzylidene)-hydrazino]-1H-quinoxalin-2-ones 3a-f and 1-(substituted-phenyl)-5H-[1,2,4]triazolo[4,3-a]quinoxalin-4-ones 4a-f. Four compounds showed promising enzyme inhibitory effect, compounds 3f and 4b-d potently inhibited the catalytic activities of all of the studied proinflammatory sPLA2. Compound 3e inhibited α-glucosidase (IC50 = 9.99 ± 0.18 µM); which is comparable to quercetin (IC50 = 9.93 ± 0.66 µM), a known inhibitor of this enzyme. Unfortunately, all compounds showed weak activity against α-amylase (IC50 > 200 µM). Structure-based molecular modelling tools were utilised to rationalise the SAR compared to co-crystal structures with sPLA2-GX as well as α-glucosidase. This report introduces novel compounds with dual activities on biochemically unrelated enzymes mutually involved in diabetes and its complications.
    Matched MeSH terms: Phospholipases A2, Secretory/antagonists & inhibitors*; Phospholipases A2, Secretory/metabolism
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