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Comparison of serum cardiac troponin T and creatine kinase MB isoenzyme mass concentrations in asphyxiated term infants during the first 48 h of life

Boo NY, Hafidz H, Nawawi HM, Cheah FC, Fadzil YJ, Abdul-Aziz BB, et al.

J Paediatr Child Health, 2005 Jul;41(7):331-7.
PMID: 16014136

This prospective study aimed to compare serum creatine kinase MB isoenzyme (CK-MB) mass concentrations and cardiac troponin T (cTnT) concentrations during the first 48 h of life in asphyxiated term infants.

Matched MeSH terms: Isoenzymes/blood
Allozyme variation in the camaenid tree snails Amphidromus atricallosus (Gould, 1843) and A. inversus (Müller, 1774)

Prasankok P, Ota H, Toda M, Panha S

Zoolog Sci, 2007 Feb;24(2):189-97.
PMID: 17409732

We examined allozyme variation in two camaenid tree snails, Amphidromus atricallosus and A. inversus, across two principal regions of Thailand and from Singapore, plus for A. inversus, one site in peninsular Malaysia. Using horizontal starch gel electrophoresis, 13 allozyme loci (11 polymorphic) were screened for A. atricallosus and 18 (5 polymorphic) for A. inversus. Heterozygosity was higher in A. atricallosus (Hexp=0.018-0.201, mean=0.085) than in A. inversus (Hexp=0-0.023, mean= 0.002). Genetic heterogeneity among samples was higher in A. inversus (Fst=0.965) than in A. atricallosus (Fst=0.781). Within A. atricallosus, populations were more differentiated in southern Thailand (Fst=0.551) than in eastern Thailand (Fst=0.144). The high Fst and low Hexp in populations of A. inversus suggest that this species is likely to have experienced a series of strong bottlenecks, perhaps occurring chiefly on offshore continental-shelf islands. The low Fst values of A. atricallosus in eastern Thailand suggest frequent gene flows among populations in this region. The southern and eastern samples of A. atricallosus exhibited fixed allele differences at four loci and great genetic distance (Nei's D=0.485-0.946), suggesting that these two samples may actually represent, or else be evolving into, separate species.

Matched MeSH terms: Isoenzymes/genetics*
Estrogen and progesterone differentially regulate carbonic anhydrase II, III, IX, XII, and XIII in ovariectomized rat uteri

Karim K, Giribabu N, Muniandy S, Salleh N

Syst Biol Reprod Med, 2016;62(1):57-68.
PMID: 26709452 DOI: 10.3109/19396368.2015.1112699

Changes in the uterus expression of carbonic anhydrase (CA) II, III, IX, XII, and XIII were investigated under the influence of sex-steroids in order to elucidate mechanisms underlying differential effects of these hormones on uterine pH. Uteri of ovariectomised rats receiving over three days either vehicle, estrogen, or progesterone or three days estrogen followed by three days either vehicle or progesterone were harvested. Messenger RNA (mRNA) and protein levels were quantified by real-time PCR and Western blotting, respectively. The distribution of CA isoenzymes proteins were examined by immunohistochemistry. The levels of CAII, III, XII, and XIII mRNAs and proteins were elevated while levels of CAIX mRNA and protein were reduced following progesterone-only and estrogen plus progesterone treatment, compared to the control and estrogen plus vehicle, respectively. Following estrogen treatment, expression of CAII, IX, XII, and CAXIII mRNAs and proteins were reduced, but remained at a level higher than control, except for CAIX, where its level was higher than the control and following progesterone treatment. Under progesterone-only and estrogen plus progesterone influences, high levels of CAII, III, XII, and XIII were observed in uterine lumenal and glandular epithelia and myometrium. However, a high level of CAIX was observed only under the influence of estrogen at the similar locations. In conclusion, high expression of CAII, III, XII, and XIII under the influence of progesterone and estrogen plus progesterone could result in the reduction of uterine tissue and fluid pH; however, the significance of high levels of CAIX expression under the influence of estrogen remains unclear.

Matched MeSH terms: Isoenzymes/metabolism
Coumarins and other fused bicyclic heterocycles with selective tumor-associated carbonic anhydrase isoforms inhibitory activity

Bozdag M, Alafeefy AM, Altamimi AM, Vullo D, Carta F, Supuran CT

Bioorg Med Chem, 2017 01 15;25(2):677-683.
PMID: 27939347 DOI: 10.1016/j.bmc.2016.11.039

Herein we report for the first time a series of 2-benzamido-N-(2-oxo-4-(methyl/trifluoromethyl)-2H-chromen-7-yl) benzamide 3a-f and substituted quinazolin-4(3H)-ones and 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (5, 6, 8 and 10a-c) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with KIs of 10.9 and 6.7nM.

Matched MeSH terms: Isoenzymes/antagonists & inhibitors; Isoenzymes/metabolism
Probing 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones as multi-target directed ligands against cholinesterases, carbonic anhydrases and α-glycosidase enzymes

Hashmi S, Khan S, Shafiq Z, Taslimi P, Ishaq M, Sadeghian N, et al.

Bioorg Chem, 2021 02;107:104554.
PMID: 33383322 DOI: 10.1016/j.bioorg.2020.104554

With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.

Matched MeSH terms: Isoenzymes/antagonists & inhibitors; Isoenzymes/metabolism
Neuromuscular effects of four phospholipases A2 from the venom of Pseudechis australis, the Australian king brown snake

Geh SL, Rowan EG, Harvey AL

Toxicon, 1992 Sep;30(9):1051-7.
PMID: 1440642

Four homologous single chain phospholipases A2 (Pa-1G, Pa-5, Pa-12C and Pa-15) were tested for neuromuscular effects on chick biventer cervicis and mouse hemidiaphragm nerve-muscle preparations. The four isozymes blocked directly elicited (mouse hemidiaphragm) and indirectly elicited (mouse and chick nerve-muscle preparations) twitch responses in concentrations of 1-30 micrograms/ml. The order of potency seen in both types of preparations was Pa-1G = Pa-5 greater than Pa-12C much greater than Pa-15. All four isozymes caused slow-onset, sustained contractures and reduction of muscle membrane potentials. In the chick preparation, responses to acetylcholine, carbachol and KCl were reduced by exposure to the toxins. It is concluded that the toxins act primarily postsynaptically to depress muscle contractility, perhaps by directly damaging muscle fibres. The order of potency agrees with their phospholipase A2 activity. Pa-1G is unusual because it is an acidic molecule, most toxic phospholipases being basic.

Matched MeSH terms: Isoenzymes/pharmacology; Isoenzymes/chemistry
Frequency of mutant CYP1A1, NAT2 and GSTM1 alleles in normal Indians and Malays

Zhao B, Lee EJ, Wong JY, Yeoh PN, Gong NH

Pharmacogenetics, 1995 Oct;5(5):275-80.
PMID: 8563767

Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.

Matched MeSH terms: Isoenzymes/genetics; Isoenzymes/metabolism
Monoterpene alcohol metabolism: identification, purification, and characterization of two geraniol dehydrogenase isoenzymes from Polygonum minus leaves

Hassan M, Maarof ND, Ali ZM, Noor NM, Othman R, Mori N

Biosci Biotechnol Biochem, 2012;76(8):1463-70.
PMID: 22878188

NADP(+)-dependent geraniol dehydrogenase (EC 1.1.1.183) is an enzyme that catalyzes the oxidation of geraniol to geranial. Stable, highly active cell-free extract was obtained from Polygonum minus leaves using polyvinylpolypyrrolidone, Amberlite XAD-4, glycerol, 2-mercaptoethanol, thiourea, and phenylmethylsulfonylfluoride in tricine-NaOH buffer (pH 7.5). The enzyme preparation was separated into two activity peaks, geraniol-DH I and II, by DEAE-Toyopearl 650M column chromatography at pH 7.5. Both isoenzymes were purified to homogeneity in three chromatographic steps. The geraniol-DH isoenzymes were similar in molecular mass, optimal temperature, and pH, but the isoelectric point, substrate specificity, and kinetic parameters were different. The K(m) values for geraniol of geraniol-DH I and II appeared to be 0.4 mM and 0.185 mM respectively. P. minus geraniol-DHs are unusual among geraniol-DHs in view of their thermal stability and optimal temperatures, and also their high specificity for allylic alcohols and NADP(+).

Matched MeSH terms: Isoenzymes/isolation & purification; Isoenzymes/chemistry
Characterisation of an alpha-galactosidase with potential relevance to ripening related texture changes

Soh CP, Ali ZM, Lazan H

Phytochemistry, 2006 Feb;67(3):242-54.
PMID: 16325871

alpha-Galactosidase (EC 3.2.1.22) from ripe papaya (Carica papaya L.) fruit was fractionated by a combination of ion exchange and gel filtration chromatography into three forms, viz., alpha-galactosidase 1, 2 and 3. The predominant isoform, alpha-gal 2, was probably a tetramer with a native molecular mass of about 170 kDa and 52 kDa-sized subunits and an estimated pI of 7.3. The subunit's N-terminal amino acid sequence shared high identity (97%) with the deduced sequence of a papaya cDNA clone encoding a putative alpha-galactosidase PAG2 as well as with an Ajuga reptans L. GGT1 clone encoding a galactan: galactan galactosyltransferase (66%). During ripening, alpha-galactosidase activity increased concomitantly with firmness loss and this increase was largely ascribed to alpha-gal 2. The protein level of alpha-gal 2 as estimated by immunoblot was low in developing fruits and generally increased with ripening. alpha-Galactosidase 2 also had the ability to markedly catalyse increased pectin solubility and depolymerisation while the polymers were still structurally attached to the cell walls mimicking, in part, the changes that occur during ripening. The close correlation between texture changes, alpha-gal 2 activity and protein levels as well as capability to modify intact cell walls suggest that the enzyme might contribute to papaya fruit softening during ripening. The purported mechanism of alpha-gal 2 action as a softening enzyme was discussed in terms of its functional capacity as a glycanase or perhaps, as a transglycosylase.

Matched MeSH terms: Isoenzymes/isolation & purification; Isoenzymes/chemistry
Synthesis, characterization, monoamine oxidase inhibition, molecular docking and dynamic simulations of novel 2,1-benzothiazine-2,2-dioxide derivatives

Ahmad S, Zaib S, Jalil S, Shafiq M, Ahmad M, Sultan S, et al.

Bioorg Chem, 2018 10;80:498-510.
PMID: 29996111 DOI: 10.1016/j.bioorg.2018.04.012

In this research work, we report the synthesis and biological evaluation of two new series of 1-benzyl-4-(benzylidenehydrazono)-3,4-dihydro-1H-benzo[c] [1,2]thiazine 2,2-dioxides and 1-benzyl-4-((1-phenylethylidene)hydrazono)-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxides. The synthetic plan involves the mesylation of methyl anthranilate with subsequent N-benzylation of the product. The methyl 2-(N-benzylmethylsulfonamido)benzoate was subjected to cyclization reaction in the presence of sodium hydride to obtain 1-benzyl-1H-benzo[c][1,2]thiazin-4(3H)-one 2,2-dioxide which was treated with hydrazine hydrate to get corresponding hydrazone precursor. Finally, the titled compounds were obtained by reaction of hydrazone with various substituted aldehydes and ketones. The synthesized derivatives were subjected to carry out their inhibition activities against monoamine oxidases along with modelling investigations to evaluate their binding interactions and dynamic stability during the docking studies. The inhibition profile of potent compounds was found as competitive for both the isozymes. The compounds were more selective inhibitors of MAO-A as compared to MAO-B. Moreover, drug likeness profile of the derivatives was evaluated to have an additional insight into the physicochemical properties. The molecular dynamic simulations predicted the behaviour of amino acids with the active site residues.

Matched MeSH terms: Isoenzymes
Synthesis, X-ray crystal and monoamine oxidase inhibitory activity of 4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine 5,5-dioxides: In vitro studies and docking analysis

Ahmad S, Jalil S, Zaib S, Aslam S, Ahmad M, Rasul A, et al.

Eur J Pharm Sci, 2019 Apr 01;131:9-22.
PMID: 30735822 DOI: 10.1016/j.ejps.2019.02.007

We report the synthesis and biological evaluation of two new series of 2-amino-6-benzyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides and 2-amino-6-methyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxides. The synthetic methodology involves a multistep reaction starting with methyl anthranilate which was coupled with methane sulfonyl chloride. The product of the reaction was subjected to N-benzylation and N-methylation reactions followed by ring closure with sodium hydride resulting in the formation of respective 2,1-benzothiazine 2,2-dioxides. These 2,1-benzothiazine precursors were subjected to multicomponent reaction with malononitrile and substituted benzaldehydes for the synthesis of two new series of pyranobenzothiazines (6a-r and 7a-r). The synthesized compounds were screened as selective inhibitors of monoamine oxidase A and monoamine oxidase B. The in vitro results suggested that compound 6d and 7q are the selective inhibitors of monoamine oxidase A, however, the selective and potent inhibitors of monoamine oxidase B included compounds 6h and 7r. Moreover, some dual inhibitors were noticed like 7l having more inhibitory activity towards both the isozymes. Moreover, the binding modes of the selective and potent inhibitors of monoamine oxidase A and B were investigated by molecular docking analysis. The results suggested that the synthetic derivatives may be potential towards the monoamine oxidase isozymes.

Matched MeSH terms: Isoenzymes
Fulltext Population genetics of Intsia palembanica (Leguminosae) and genetic conservation of Virgin Jungle Reserves in Peninsular Malaysia

Lee SL, Ng KK, Saw LG, Norwati A, Salwana MH, Lee CT, et al.

Am J Bot, 2002 Mar;89(3):447-59.
PMID: 21665641 DOI: 10.3732/ajb.89.3.447

A field survey of Virgin Jungle Reserve (VJR) compartments in Peninsular Malaysia allowed us to identify six populations of Intsia palembanica for this study. These were Pasoh Forest Reserve (FR) (Pasoh), Sungai Lalang FR (Lalang), Bukit Lagong FR (Lagong), Bubu FR (Bubu), Bukit Kinta FR (Kinta), and Bukit Perangin FR (Perangin). About 40 adult individuals were sampled in each population. In addition, progeny arrays were collected from nine mother plants at Lagong for a mating system study. A total of nine allozymes, encoded by 14 putative gene loci, were consistently resolved in I. palembanica. The mating system study showed that the species exhibited a mixed-mating system, with multilocus outcrossing rate of 0.766. The levels of diversity were comparably high (mean number of alleles per polymorphic locus = 2.4, mean effective number of alleles per polymorphic locus = 1.64, and mean expected heterozygosity (H(e)) = 0.242), and the majority of the diversity was partitioned within population (G(ST) = 0.040 and F(ST) = 0.048). Significant levels of inbreeding were detected in Bubu and Perangin. Probability tests of recent effective population size reduction using the Infinite Allele Model showed the occurrence of genetic bottlenecks on Lalang and Kinta. Two genetically unique populations (Pasoh and Perangin) were inferred using jackknife analysis. By using the neutral mutation rates, effective population size (N(e)) to maintain the H(e) was 80-800 000 individuals. A simulation study based on pooled samples, however, circumscribed the N(e) to 200 and 210 individuals. Implications of the study for managing the species and the VJRs are discussed.

Matched MeSH terms: Isoenzymes
Fulltext Acute myocardial injury: an entity of acute coronary syndromes

Daud MS, Khalid Y

Med J Malaysia, 1997 Jun;52(2):183-5.
PMID: 10968081

A 46-year-old Indian man was admitted with unstable angina (Braunwald's class IIIB1)--the chest pain at rest was associated with inferolateral ischaemia on the ECG at admission. His serial total creatine kinase levels were elevated but CKMB was not detected. Serial serum troponin T levels were significantly raised suggesting the presence of significant acute myocardial injury.

Matched MeSH terms: Isoenzymes
Caspase-dependent and -independent mechanisms in apoptosis induced by hydroquinone and catechol metabolites of remoxipride in HL-60 cells

Inayat-Hussain SH, McGuinness SM, Johansson R, Lundstrom J, Ross D

Chem Biol Interact, 2000 Aug 15;128(1):51-63.
PMID: 10996300

The hydroquinone and catechol like metabolites, NCQ344 and NCQ436 respectively, of the antipsychotic remoxipride have recently been demonstrated to induce apoptosis in myeloperoxidase (MPO)-rich human bone marrow progenitor and HL-60 cells [S.M. McGuinness, R. Johansson, J. Lundstrom, D. Ross, Induction of apoptosis by remoxipride metabolites in HL-60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia, Chem. Biol. Interact. 121 (1999) 253-265]. In the present study, we determined the molecular mechanisms of apoptosis induced by these remoxipride metabolites in HL-60 cells. Our results show that apoptosis was accompanied by phosphatidylserine (PS) exposure, activation of caspases-9, -3, -7 and DNA cleavage. In HL-60 cells treated with the hydroquinone NCQ344 and catechol NCQ436, the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp. fluoromethyl ketone (Z-VAD.FMK) blocked DNA cleavage and activation of caspases-9, -3/-7. In addition, PS exposure was significantly but not completely inhibited by Z-VAD.FMK. These results demonstrate that although Z-VAD.FMK inhibitable caspases are necessary for maximal apoptosis induced by NCQ344 and NCQ436, additional caspase-independent processes may orchestrate changes leading to PS exposure during apoptosis induced by the remoxipride polyphenolic metabolites.

Matched MeSH terms: Isoenzymes/antagonists & inhibitors; Isoenzymes/metabolism; Isoenzymes/physiology
Fulltext Validation of Faecal Pyruvate Kinase Isoenzyme Type M2 (Faecal M2PK Quick) Test in Detection of Colorectal Adenoma and Adenocarcinoma Among High-Risk Malaysian Population

Mohd Suan MA, Ng YZ, Henry GF, Md Said R, Kollanthavelu S, Mustapha MI, et al.

Asian Pac J Cancer Prev, 2023 Sep 01;24(9):3183-3186.
PMID: 37774070 DOI: 10.31557/APJCP.2023.24.9.3183

BACKGROUND: Colorectal neoplasia is a multistep process that can lead to the development of colorectal cancer. Colonoscopy is the gold standard for diagnosis and screening of colorectal cancer, but its uptake is often hindered by unpleasant experiences and logistic obstacles. Therefore, non-invasive biomarker tests such as the M2-pyruvate kinase (M2PK) test have been explored as a potential screening tool.
OBJECTIVE: This study aims to evaluate the efficacy of the M2PK Quick Stool Test (ScheBo®) in detecting colorectal adenoma and adenocarcinoma in high-risk Malaysian populations using colonoscopy as the comparison.
METHODS: A prospective, cross-sectional, multicenter study was conducted from December 2017 to December 2019 in four hospitals in Malaysia. Participants were eligible if they met any of the following criteria: personal or family history of colorectal polyps or cancer, inherited syndromes, altered bowel habits, rectal bleeding, unintended weight loss, loss of appetite, abdominal pain or cramps, or unexplained iron deficiency, or an Asia-Pacific Colorectal Screening score of 4-7. Participants provided a stool sample that was tested for M2PK using the M2PK Quick Test. Participants then underwent a colonoscopy, and any lesions found were biopsied and sent for histopathological examination.
RESULTS: A total of 562 participants were included in the study, of whom 89 had a positive M2PK test. Presence of adenoma and/or dysplastic lesions were confirmed in 14.4% and adenocarcinoma in 3.0% of the participants. The M2PK Quick Stool Test showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 58.8%, 85.5%, 11.2% and 98.5%, respectively in detecting colorectal adenocarcinoma. For detection of colorectal adenoma, this test yielded a sensitivity, specificity, PPV and NPV of 27.3%, 86.3%, 27.0% and 86.5%, respectively.
CONCLUSIONS: The M2PK Quick Stool Test showed a moderate accuracy in detecting colorectal adenocarcinoma and adenomas in the studied population.

Matched MeSH terms: Isoenzymes
A Comprehensive Review on L-Asparaginase and Its Applications

Batool T, Makky EA, Jalal M, Yusoff MM

Appl Biochem Biotechnol, 2016 Mar;178(5):900-23.
PMID: 26547852 DOI: 10.1007/s12010-015-1917-3

L-asparaginase (LA) catalyzes the degradation of asparagine, an essential amino acid for leukemic cells, into ammonia and aspartate. Owing to its ability to inhibit protein biosynthesis in lymphoblasts, LA is used to treat acute lymphoblastic leukemia (ALL). Different isozymes of this enzyme have been isolated from a wide range of organisms, including plants and terrestrial and marine microorganisms. Pieces of information about the three-dimensional structure of L-asparaginase from Escherichia coli and Erwinia sp. have identified residues that are essential for catalytic activity. This review catalogues the major sources of L-asparaginase, the methods of its production through the solid state (SSF) and submerged (SmF) fermentation, purification, and characterization as well as its biological roles. In the same breath, this article explores both the past and present applications of this important enzyme and discusses its future prospects.

Matched MeSH terms: Isoenzymes
Fulltext MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme

Malagobadan S, Ho CS, Nagoor NH

Cancer Biol Med, 2020 Feb 15;17(1):101-111.
PMID: 32296579 DOI: 10.20892/j.issn.2095-3941.2019.0010

Objective: Anoikis is apoptosis that is induced when cells detach from the extracellular matrix and neighboring cells. As anoikis serves as a regulatory barrier, cancer cells often acquire resistance towards anoikis during tumorigenesis to become metastatic. MicroRNAs (miRNAs) are short strand RNA molecules that regulate genes post-transcriptionally by binding to mRNAs and reducing the expression of its target genes. This study aimed to elucidate the role of a novel miRNA, miR-6744-5p, in regulating anoikis in breast cancer and identify its target gene. Methods: An anoikis resistant variant of the luminal A type breast cancer MCF-7 cell line (MCF-7-AR) was generated by selecting and amplifying surviving cells after repeated exposure to growth in suspension. MiRNA microarray analysis identified a list of dysregulated miRNAs from which miR-6744-5p was chosen for overexpression and knockdown studies in MCF-7. Additionally, the miRNA was also overexpressed in a triple-negative breast cancer cell line, MDA-MB-231, to evaluate its ability to impair the metastatic potential of breast cancer cells. Results: This study showed that overexpression and knockdown of miR-6744-5p in MCF-7 increased and decreased anoikis sensitivity, respectively. Similarly, overexpression of miR-6744-5p in MDA-MB-231 increased anoikis and also decreased tumor cell invasion in vitro and in vivo. Furthermore, NAT1 enzyme was identified and validated as the direct target of miR-6744-5p. Conclusions: This study has proven the ability of miR-6744-5p to increase anoikis sensitivity in both luminal A and triple negative breast cancer cell lines, highlighting its therapeutic potential in treating breast cancer.

Matched MeSH terms: Isoenzymes/genetics*
Fulltext Autoimmune markers in young Malaysian patients with type 1 diabetes mellitus

Nazaimoon WM, Azmi KN, Rasat R, Ismail IS, Singaraveloo M, Wan Mohamad WB, et al.

Med J Malaysia, 2000 Sep;55(3):318-23.
PMID: 11200711

This study determined the prevalence and significance of autoantibodies to GAD65 (GAD Ab), insulin (IAA), tyrosine-like phosphatase (IA2) and islet-cell (ICA) in a group of 213 young Malaysian Type 1 diabetics, diagnosed before the age of 40 years. Venous blood was taken at fasting, and at 6 minutes post-glucagon (1 mg i.v.). IAA was detected in 47.4%, GAD Ab in 33.8%, IA2 in 8.9% and ICA in 1.4% of the subjects. When based on post-glucagon C-peptide level of 600 pmol/L, 172 (80.7%) patients had inadequate pancreatic reserve, while the remainder 41(19.3%) showed normal response. The autoantibodies, either alone or in combination, were detectable in both groups of patients; higher prevalence in those with poor or no beta-cell function (73.3% versus 46.3%, p = 0.0001). Although the prevalence of GAD Ab was highest in newly diagnosed patients (< 5 years), unlike IA2 and ICA, the marker remained detectable in 24-25% of those patients with long-standing disease. Nineteen patients could probably belong to the "latent autoimmune diabetes in adults (LADA)" subset, where pancreatic reserve was adequate but patients had detectable autoantibodies and insulin-requiring. On the other hand, 68 of the 213 patients (32%) were seronegative, but presented with near or total beta-cell destruction. Thus, as has also been suggested by others, there is indeed etiological differences between the Asian and the Caucasian Type 1 diabetics, and, there is also the possibility that other, but unknown autoantigens are involved in causing the pancreatic damage.

Matched MeSH terms: Isoenzymes/immunology
Palm vitamin E is comparable to alpha-tocopherol in maintaining bone mineral density in ovariectomised female rats

Norazlina M, Ima-Nirwana S, Gapor MT, Khalid BA

Exp. Clin. Endocrinol. Diabetes, 2000;108(4):305-10.
PMID: 10961363

Vitamin E has been shown to affect bone metabolism. In this study we determined the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague-Dawley female rats fed with normal rat chow were divided into 4 groups and supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not supplemented. Half of these rats were ovariectomised before supplementation was given for 10 months. As expected, bone mineral density of the ovariectomised rats fed on normal rat chow diet was lower compared to the intact rats. However, these changes were not seen in the supplemented group of rats. Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a lower bone calcium content in both femoral and vertebral bones whilst rats fed palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were able to maintain bone calcium content. Alkaline phosphatase activity was elevated in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha-tocopherol also reduced the activity of tartrate-resistant acid phosphatase post-ovariectomy. These findings indicate that both palm vitamin E and alpha-tocopherol maintained bone mineral density in ovariectomised rats but caused conflicting effects on bone calcium content. Further study is needed in order to determine the mechanisms involved.

Matched MeSH terms: Isoenzymes/metabolism
Expression of placental proteins in complete and partial hydatidiform moles

Cheah PL, Looi LM

Pathology, 1994 Apr;26(2):115-8.
PMID: 8090580

Examination of routinely stained haematoxylin and eosin sections may sometimes prove inadequate in differentiating partial hydatidiform moles (PHM) from complete hydatidiform moles (CHM). While cytogenetic analysis can aid in the distinction, such facilities are not always available. The possibility of using immunohistochemistry to aid in the differentiation was studied. Twenty-five histologically proven CHM and 11 PHM were studied for their patterns of expression of human chorionic gonadotrophin (hCG), human placental lactogen (hPL) and placental alkaline phosphatase (PIAP). All CHM stained diffusely with hCG and focally with both hPL and PIAP irrespective of gestational age. Of PHM, 63.6% were diffusely positive for hCG, 27.3% for hPL and 54.5% for PIAP; the rest were focally positive. The hCG pattern changed from diffuse to focal with increasing gestational age of PHM, while those of hPL and PIAP became increasingly diffuse with gestational age. While these protein expressions may be applied in differentiating late PHM from CHM, it is not useful in first trimester cases. The most helpful application is that focal expression of hCG and diffuse expressions of hPL and PIAP is not seen in CHM, thereby excluding such a diagnosis. PHM, in contrast, can show either diffuse or focal expression of all 3 antigens.

Matched MeSH terms: Isoenzymes/analysis*

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