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A comparative study of the biological properties of Dendroaspis (mamba) snake venoms

Tan NH, Arunmozhiarasi A, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1991;99(3):463-6.
PMID: 1685421

1. The biological properties of twelve samples of venoms from all four species of Dendroaspis (mamba) were investigated. 2. Dendroaspis venoms generally exhibited very low levels of protease, phosphodiesterase and alkaline phosphomonoesterase; low to moderately low level of 5'-nucleotidase and very high hyaluronidase activities, but were devoid of L-amino acid oxidase, phospholipase A, acetylcholinesterase and arginine ester hydrolase activities. The unusual feature in venom enzyme content can be used to distinguish Dendroaspis venoms from other snake venoms. 3. All Dendroaspis venoms did not exhibit hemorrhagic or procoagulant activity. Some Dendroaspis venoms, however, exhibited strong anticoagulant activity. The intravenous median lethal dose of the venoms ranged from 0.5 microgram/g mouse to 4.2 micrograms/g mouse. 4. Venom biological activities are not very useful for the differentiation of the Dendroaspis species. The four Dendroaspis venoms, however, can be differentiated by their venom SDS-polyacrylamide gel electrophoretic patterns.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
The activation of chick alkaline phosphatase by calmodulin

Sivanaesan L, Kwan TK, Perumal R

Biochem. Int., 1991 Oct;25(3):561-70.
PMID: 1666829

Calmodulin, an activator protein in most calcium-dependent processes, was isolated to apparent homogeneity from the femurs of 1-day old chicks using phenyl-Sepharose and high performance liquid chromatography. The purified calmodulin was found to produce a 6-fold increase in the activity of alkaline phosphatase isolated from the same source. A Ca2+ concentration of 10(-5) M was required for the activation. Purification of alkaline phosphatase involved acetone precipitation, DEAE-Sephacel and Sephadex G-200 column chromatography. The enzyme was purified to 540-fold and had a specific activity of 10.75 U/mg protein.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
Protein-Protein Interactions of Phosphodiesterases

Al-Nema MY, Gaurav A

Curr Top Med Chem, 2019;19(7):555-564.
PMID: 30931862 DOI: 10.2174/1568026619666190401113803

BACKGROUND: Phosphodiesterases (PDEs) are enzymes that play a key role in terminating cyclic nucleotides signalling by catalysing the hydrolysis of 3', 5'- cyclic adenosine monophosphate (cAMP) and/or 3', 5' cyclic guanosine monophosphate (cGMP), the second messengers within the cell that transport the signals produced by extracellular signalling molecules which are unable to get into the cells. However, PDEs are proteins which do not operate alone but in complexes that made up of a many proteins.
OBJECTIVE: This review highlights some of the general characteristics of PDEs and focuses mainly on the Protein-Protein Interactions (PPIs) of selected PDE enzymes. The objective is to review the role of PPIs in the specific mechanism for activation and thereby regulation of certain biological functions of PDEs.
METHODS: The article discusses some of the PPIs of selected PDEs as reported in recent scientific literature. These interactions are critical for understanding the biological role of the target PDE.
RESULTS: The PPIs have shown that each PDE has a specific mechanism for activation and thereby regulation a certain biological function.
CONCLUSION: Targeting of PDEs to specific regions of the cell is based on the interaction with other proteins where each PDE enzyme binds with specific protein(s) via PPIs.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism*
A comparative study of the biological properties of venoms from snakes of the genus Vipera (true adders)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1990;96(4):683-8.
PMID: 2171867

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, hyaluronidase, alkaline phosphomonoesterase, 5'-nucleotidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 26 samples of venoms of 13 taxa of Vipera were determined and the Sephadex G-75 gel filtration patterns for some of the venoms were also examined. 2. The results indicate the presence of certain common characteristics among the venoms, particularly if V. russelli is excluded from the comparison. The results also support the recently proposed reassignment of V. russelli to a separate genus. 3. The data show that information on venom biological properties can be used for differentiation of venoms of many species of Vipera. Particularly useful for this purpose are the protease, phosphodiesterase, phospholipase A and the procoagulant activities and the Sephadex G-75 gel filtration patterns of the venoms.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
Discovery of natural product inhibitors of phosphodiesterase 10A as novel therapeutic drug for schizophrenia using a multistep virtual screening

Al-Nema M, Gaurav A, Akowuah G

Comput Biol Chem, 2018 Dec;77:52-63.
PMID: 30240986 DOI: 10.1016/j.compbiolchem.2018.09.001

The major complaint that most of the schizophrenic patients' face is the cognitive impairment which affects the patient's quality of life. The current antipsychotic drugs treat only the positive symptoms without alleviating the negative or cognitive symptoms of the disease. In addition, the existing therapies are known to produce extrapyramidal side effects that affect the patient adherence to the treatment. PDE10A inhibitor is the new therapeutic approach which has been proven to be effective in alleviating the negative and cognitive symptoms of the disease. A number of PDE10A inhibitors have been developed, but no inhibitor has made it beyond the clinical trials so far. Thus, the present study has been conducted to identify a PDE10A inhibitor from natural sources to be used as a lead compound for the designing of novel selective PDE10A inhibitors. Ligand and structure-based pharmacophore models for PDE10A inhibitors were generated and employed for virtual screening of universal natural products database. From the virtual screening results, 37 compounds were docked into the active site of the PDE10A. Out of 37 compounds, three inhibitors showed the highest affinity for PDE10A where UNPD216549 showed the lowest binding energy and has been chosen as starting point for designing of novel PDE10A inhibitors. The structure-activity-relationship studies assisted in designing of selective PDE10A inhibitors. The optimization of the substituents on the phenyl ring resulted in 26 derivatives with lower binding energy with PDE10A as compared to the lead compound. Among these, MA 8 and MA 98 exhibited the highest affinity for PDE10A with binding energy (-10.90 Kcal/mol).

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism*
A comparative study of the biological activities of rattlesnake (genera Crotalus and Sistrurus) venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1991;98(2-3):455-61.
PMID: 1676959

1. The hemorrhagic, procoagulant, anticoagulant, protease, arginine ester hydrolase, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, phospholipase A and L-amino acid oxidase activities of 50 venom samples from 20 taxa of rattlesnake (genera Crotalus and Sistrurus) were examined. 2. The results show that notwithstanding individual variations in the biological activities of Crotalus venoms and the wide ranges of certain biological activities observed, there are some common characteristics at the genus and species levels. 3. The differences in biological activities of the venoms compared can be used for differentiation of the species. Particularly useful for this purpose are the thrombin-like enzyme, protease, arginine ester hydrolase, hemorrhagic and phospholipase A activities and kaolin-cephalin clotting time measurements.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
A comparative study of the enzymatic and toxic properties of venoms of the Asian lance-headed pit viper (Genus Trimeresurus)

Tan NH, Armugam A, Tan CS

Comp. Biochem. Physiol., B, 1989;93(4):757-62.
PMID: 2553329

1. The lethalities, anticoagulant effects, hermorrhagic, thrombin-like enzyme, hyaluronidase, protease, arginine ester hydrolase, 5'-nucleotidase, L-amino acid oxidase, alkaline phosphomonoesterase, phosphodiesterase and phospholipase A activities of twenty-three samples of venoms from twelve species of Asian lance-headed pit vipers (genus Trimeresurus) were examined. 2. The results indicate that notwithstanding individual variations in venom properties, the differences in biological properties of the Trimeresurus venoms can be used for the differentiation of venoms from different species of Trimeresurus. 3. The results also suggest that differences in the biological properties of snake venoms are useful parameters in the classification of snake species. 4. Our results indicate that venoms from the species T. okinavensis exhibited biological properties markedly different from other Trimeresurus venoms examined. This observation supports the recently proposed reclassification of T. okinavensis as a member of the genus Ovophis, rather than the genus Trimeresurus.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
A comparative study of the biological activities of venoms from snakes of the genus Agkistrodon (moccasins and copperheads)

Tan NH, Ponnudurai G

Comp. Biochem. Physiol., B, 1990;95(3):577-82.
PMID: 2158874

1. The hemorrhagic, procoagulant, anticoagulant, phosphodiesterase, alkaline phosphomonoesterase, 5'-nucleotidase, hyaluronidase, arginine ester hydrolase, phospholipase A, L-amino acid oxidase and protease activities of 31 samples of venom from three species of Agkistrodon (A. bilineatus, A. contortrix and A. piscivorus) and 10 venom samples from five other related species belonging to the same tribe of Agkistrodontini were examined. 2. The results indicate that interspecific differences in certain biological activities of the Agkistrodon venoms are more marked than individual variations of the activities, and that these differences can be used for differentiation of the species. Particularly useful for this purpose are the phosphodiesterase, arginine ester hydrolase and anticoagulant activities of the venoms. 3. Venoms of the subspecies of A. contortrix and A. piscivorus do not differ significantly in their biological activities.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
A comparative study of the biological properties of krait (genus Bungarus) venoms

Tan NH, Ponnudurai G

Comp Biochem Physiol C Comp Pharmacol Toxicol, 1990;95(1):105-9.
PMID: 1971550

1. The intravenous median lethal doses (LD50), protease, phosphodiesterase, alkaline phosphomonoesterase, L-amino acid oxidase, acetylcholinesterase, phospholipase A, 5'-nucleotidase, hyauronidase and anticoagulant activities of fourteen samples of venoms from the four common species of krait (Bungarus caeruleus, Bungarus candidus, Bungarus multicinctus and Bungarus fasciatus) were examined. 2. The results indicate that even though there are individual variations in the biological properties of the krait venoms, interspecific differences in the properties can be used for differentiation of the venoms from the four species of Bungarus. Particularly useful for this purpose are the LD50's and the contents of 5'-nucleotidase and hyaluronidase of the venoms.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
Electrophoretic profiles and biological activities: intraspecific variation in the venom of the Malayan pit viper (Calloselasma rhodostoma)

Daltry JC, Ponnudurai G, Shin CK, Tan NH, Thorpe RS, Wüster W

Toxicon, 1996 Jan;34(1):67-79.
PMID: 8835335

The Malayan pit viper (Calloselasma rhodostoma) is of major clinical significance both as a leading cause of snakebite and as the source of ancrod (Arvin). Although its venom has been extensively studied, the degree to which venom composition varies between individuals is poorly known. We individually analysed the venoms of over 100 C. rhodostoma using isoelectric focusing. In all populations, females produced an intense band that was absent from all males, and significant ontogenetic variation was detected. Principal components analysis of the banding profiles also revealed strong geographic variation, which was significantly congruent with variation in the biological activities of the venom (phosphodiesterase, alkalinephosphoesterase, L-amino acid oxidase, arginine ester hydrolase, 5'-nucleotidase, thrombin-like enzyme, haemorrhagic activity). Studies of captive-bred snakes indicate that the intraspecific variation in venom is genetically inherited rather than environmentally induced. The intraspecific variation in venom composition and biological activity could be of applied importance to snakebite therapy, both in correct diagnosis of the source of envenomation and in the development of a more effective antivenom. Greater attention should be given to the source of C. rhodostoma venom used in research to ensure reproducibility of results.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism
Fulltext Effect of postoperative corticosteroids on surgical outcome and aqueous autotaxin following combined cataract and microhook ab interno trabeculotomy

Honjo M, Yamagishi R, Igarashi N, Ku CY, Kurano M, Yatomi Y, et al.

Sci Rep, 2021 01 12;11(1):747.
PMID: 33436915 DOI: 10.1038/s41598-020-80736-w

To evaluate the effect of postoperative corticosteroids on surgical outcome and autotaxin (ATX) levels after microhook ab interno trabeculotomy combined with cataract surgery (μLOT-CS), prospective, consecutive non-randomized case series comparing outcomes of 30 eyes with primary open angle glaucoma was performed. The aqueous ATX, intraocular pressure (IOP) and glaucoma medications were monitored for 3 months postoperatively. An in-vivo mouse μLOT model was generated. In vitro, ATX and fibrotic changes induced by dexamethasone (Dex) treatment following scratch (S) in cultured human trabecular meshwork (hTM) cells were assessed by immunofluorescence, immunoenzymatic assay, and RT-qPCR. Postoperative ATX at 1 week and the number of antiglaucoma medications at 3 months were significantly lower in non-steroid group, and steroid use was the only variable significantly associated with postoperative medications at 3 months in multiregression analyses. In vitro, ATX activity was significantly upregulated in the Dex + S group, and αSMA was significantly upregulated in the Dex and Dex + S groups. Fibronectin and COL1A1 were significantly upregulated in the S group. μLOT-CS decreased IOP and medications in the overall cohort, and non-use of postoperative steroids resulted in a smaller number of postoperative medications. Limiting postoperative steroids in μLOT may minimize IOP elevation and postoperative fibrosis.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism*
Eurycomanone, the major quassinoid in Eurycoma longifolia root extract increases spermatogenesis by inhibiting the activity of phosphodiesterase and aromatase in steroidogenesis

Low BS, Choi SB, Abdul Wahab H, Das PK, Chan KL

J Ethnopharmacol, 2013 Aug 26;149(1):201-7.
PMID: 23810842 DOI: 10.1016/j.jep.2013.06.023

Eurycoma longifolia Jack (Simaroubaceae family), known locally as 'Tongkat Ali' by the ethnic population, is popularly taken as a traditional remedy to improve the male libido, sexual prowess and fertility. Presently, many tea, coffee and carbonated beverages, pre-mixed with the root extract are available commercially for the improvement of general health and labido. Eurycomanone, the highest concentrated quassinoid in the root extract of E. longifolia improved fertility by increasing testosterone and spermatogenesis of rats through the hypothalamus-pituitary-gonadal axis, but the mechanisms underlying the effects are not totally clear.

Matched MeSH terms: Phosphoric Diester Hydrolases/metabolism

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