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1.
Community Dent Health ; 39(2): 92-98, 2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34982863

RESUMEN

OBJECTIVES: To assess the psychometric properties, including face, content, criterion and known-groups validity and reliability, of scales to measure oral health-related self-efficacy and fatalism in a regional Aboriginal adult population in Australia. METHODS: Four hundred Aboriginal adults (aged 18-82 years, 67% female) completed a self-report questionnaire including items pertaining to oral health-related self-efficacy and fatalism. Structural validity was determined in exploratory factor analysis (EFA) with principal components analysis for each scale. Criterion validity was assessed between the instruments and theoretically related variables. Known-groups validity was investigated by comparing the scores in different population groups according to age, sex, education and employment. Reliability of the scales was assessed through internal consistency. RESULTS: The EFA confirmed a single factor structure for self-efficacy and fatalism scales, with Cronbach's alphas of 0.93 and 0.89 respectively. The two scales were not correlated. Oral health-related self-efficacy was associated with toothbrush ownership and brushing the previous day supporting criterion validity. Oral health-related fatalism was associated with previous extractions and perceived need for extractions also supporting criterion validity. Both measures were associated with social impact of oral health as measured by the OHIP-14, supporting their criterion validity. Mixed findings were observed in terms of known-groups validity. CONCLUSIONS: There was initial evidence that measures of oral health-related self-efficacy and fatalism displayed adequate psychometric properties in this Aboriginal community. These constructs could have implications for approaches for improving oral health among Aboriginal people.


Asunto(s)
Salud Bucal , Autoeficacia , Adulto , Australia , Femenino , Humanos , Masculino , Psicometría , Reproducibilidad de los Resultados , Australia del Sur , Encuestas y Cuestionarios
2.
Community Dent Health ; 32(2): 111-6, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26263605

RESUMEN

UNLABELLED: Stage of Change constructs may be proxy markers of psychosocial health which, in turn, are related to oral health. OBJECTIVE: To determine if Stage of Change constructs were associated with subjective oral health in a population at heightened risk of dental disease. METHODS: Stage of Change constructs were developed from a validated 18-item scale and categorised into 'Pre-contemplative', 'Contemplative' and 'Active'. A convenience sample of 446 Australian non-Aboriginal women pregnant by an Aboriginal male (age range 14-43 years) provided data to evaluate the outcome variables (self-rated oral health and oral health impairment), the Stage of Change constructs and socio-demographic, behavioural and access-related factors. Factors significant at the p < 0.05 level in bivariate analysis were entered into prevalence regression models. RESULTS: Approximately 54% of participants had fair/poor self-rated oral health and 34% had oral health impairment. Around 12% were 'Pre-contemplative', 46% 'Contemplative' and 42% 'Active'. Being either 'pre-contemplative' or 'contemplative' was associated with poor self-rated oral health after adjusting for socio-demographic factors. 'Pre-contemplative' ceased being significant after adjusting for dentate status and dental behaviour. 'Pre-contemplative' remained significant when adjusting for dental cost, but not 'Contemplative'. The Stages of Change constructs ceased being associated with self-rated oral health after adjusting for all confounders. Only 'Contemplative' (reference: 'Active') was a risk indicator in the null model for oral health impairment which persisted after adding dentate status, dental behaviour and dental cost variables, but not socio-demographics. When adjusting for all confounders, 'Contemplative' was not a risk indicator for oral health impairment. CONCLUSIONS: Both the 'Pre-contemplative' and 'Contemplative' Stage of Change constructs were associated with poor self-rated oral health and oral health impairment after adjusting for some, but not all, covariates. When considered as a proxy marker of psychosocial health, Stage of Change constructs may have some relevance for subjective oral health.


Asunto(s)
Actitud Frente a la Salud , Conductas Relacionadas con la Salud , Salud Bucal , Mujeres Embarazadas/psicología , Autoimagen , Poblaciones Vulnerables , Adolescente , Adulto , Factores de Edad , Automóviles , Ansiedad al Tratamiento Odontológico/psicología , Atención Odontológica/economía , Atención Odontológica/psicología , Escolaridad , Familia , Conducta Alimentaria , Femenino , Humanos , Renta , Nativos de Hawái y Otras Islas del Pacífico , Propiedad , Embarazo , Clase Social , Enfermedades Dentales/psicología , Extracción Dental/psicología , Cepillado Dental/psicología , Adulto Joven
3.
Community Dent Health ; 31(3): 167-71, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25300152

RESUMEN

OBJECTIVE: To better understand the determinants of self-rated oral health within an Indigenous population by: 1, examining potential individual-level correlates of socio-demographic, health behaviours, dental care access and oral health literacy-related outcomes with self-rated oral health; and, 2, examining the relative contribution of these domains to self-rated oral health in multivariable modelling. METHODS: We conducted nested logistic regression analyses on self-reported status of 'fair or poor' versus 'better' oral health using data from a convenience sample of rural dwelling Indigenous Australians (n = 468). Data were collected on background characteristics, health behaviours, access to dental care, oral health literacy-related outcome variables and REALD 30, an oral health literacy scale. RESULTS: Overall 37.0 % of the Indigenous adult population reported fair or poor oral health. In multivariable modelling, risk indicators for fair or poor self-rated oral health that persisted after adjusting for other covariates included being aged 38+ years (OR 2.9, 95%CI 1.9,4.6), holding a Government Health Concession card (OR 2.3, 95%CI 1.1,4.5), avoiding the dentist due to financial constraints (OR 2.3, 95%CI 1.4,3.6), not knowing how to make an emergency dental visit (OR 1.7, 95%CI 1.1,2.7) and poor understanding of the prevention of dental disease (OR 1.7, 95%CI 1.1,2.7). CONCLUSIONS: In this vulnerable population, risk indicators contributing to poor self-rated oral health included socio-demographic, dental care access and oral health literacy-related factors. Health behaviours were not significant.


Asunto(s)
Atención Odontológica , Conductas Relacionadas con la Salud , Alfabetización en Salud , Accesibilidad a los Servicios de Salud , Nativos de Hawái y Otras Islas del Pacífico , Salud Bucal , Adulto , Factores de Edad , Australia , Caries Dental/prevención & control , Tratamiento de Urgencia , Femenino , Costos de la Atención en Salud , Humanos , Seguro de Salud , Masculino , Factores de Riesgo , Salud Rural , Autoinforme , Factores Socioeconómicos , Cepillado Dental , Poblaciones Vulnerables
4.
Community Dent Health ; 31(3): 145-52, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25300148

RESUMEN

OBJECTIVES: Despite burgeoning evidence regarding the pathways by which experiences of racism influence health outcomes, little attention has been paid to the relationship between racism and oral health-related behaviours in particular. We hypothesised that self-reported racism was associated with tooth brushing, and that this association was mediated by perceived stress and sense of control and moderated by social support. METHODS: Data from 365 pregnant Aboriginal Australian women were used to evaluate tooth brushing behaviour, sociodemographic factors, psychosocial factors, general health, risk behaviours and racism exposure. Bivariate associations were explored and hierarchical logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for tooth brushing. Perceived stress and sense of control were examined as mediators of the association between self-reported racism and tooth brushing using binary mediation with bootstrapping. RESULTS: High levels of self-reported racism persisted as a risk indicator for tooth brushing (OR 0.51, 95%CI 0.27,0.98) after controlling for significant covariates. Perceived stress mediated the relationship between self-reported racism and tooth brushing: the direct effect of racism on tooth brushing was attenuated, and the indirect effect on tooth brushing was significant (beta coefficient -0.09; bias-corrected 95%CI -0.166,-0.028; 48.1% of effect mediated). Sense of control was insignificant as a mediator of the relationship between racism and tooth brushing. CONCLUSIONS: High levels of self-reported racism were associated with non-optimal tooth brushing behaviours, and perceived stress mediated this association among this sample of pregnant Aboriginal women.. Limitations and implications are discussed.


Asunto(s)
Nativos de Hawái y Otras Islas del Pacífico/psicología , Embarazo/psicología , Racismo/psicología , Cepillado Dental/psicología , Adolescente , Adulto , Australia , Automóviles , Escolaridad , Femenino , Conductas Relacionadas con la Salud , Estado de Salud , Humanos , Seguro de Salud , Control Interno-Externo , Salud Bucal , Asunción de Riesgos , Autoimagen , Autoinforme , Clase Social , Apoyo Social , Estrés Psicológico/psicología , Población Urbana , Adulto Joven
5.
Community Dent Health ; 30(1): 52-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23550508

RESUMEN

OBJECTIVES: To compare oral health literacy (OHL) levels between two profoundly disadvantaged groups, Indigenous Australians and American Indians, and to explore differences in socio-demographic, dental service utilisation, self-reported oral health indicators, and oral health-related quality of life (OHRQoL) correlates of OHL among the above. METHODS: OHL was measured using REALD-30 among convenience samples of 468 Indigenous Australians (aged 17-72 years, 63% female) and 254 female American Indians (aged 18-57 years). Covariates included socio-demography, dental utilisation, self-reported oral health status (OHS), perceived treatment needs and OHRQoL (prevalence, severity and extent of OHIP-14 'impacts'). Descriptive and bivariate methods were used for data presentation and analysis, and between-sample comparisons relied upon empirical contrasts of sample-specific estimates and correlation coefficients. RESULTS: OHL scores were: Indigenous Australians - 15.0 (95% CL=14.2, 15.8) and American Indians--13.7 (95% CL=13.1, 14.4). In both populations, OHL strongly correlated with educational attainment, and was lower among participants with infrequent dental attendance and perceived restorative treatment needs. A significant inverse association between OHL and prevalence of OHRQoL impacts was found among American Indians (rho=-0.23; 95% CL = -0.34, -0.12) but not among Indigenous Australians. CONCLUSIONS: Our findings indicate that OHL levels were comparable between the two groups and lower compared to previously reported estimates among diverse populations. Although the patterns of association of OHL with most examined domains of correlates were similar between the two groups, this study found evidence of heterogeneity in the domains of self-reported OHS and OHRQoL.


Asunto(s)
Alfabetización en Salud/estadística & datos numéricos , Indígenas Norteamericanos/estadística & datos numéricos , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Salud Bucal/estadística & datos numéricos , Adolescente , Adulto , Anciano , Australia , Intervalos de Confianza , Servicios de Salud Dental/estadística & datos numéricos , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Autoinforme , Perfil de Impacto de Enfermedad , Estados Unidos , Poblaciones Vulnerables , Adulto Joven
6.
Aust Dent J ; 67(2): 132-137, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34862620

RESUMEN

BACKGROUND: In Australia, Aboriginal adults experience higher levels of poor oral and general health than the non-Aboriginal population. This study compared self-rated oral and general health among Aboriginal adults in regional South Australia with participants in the National Survey of Adult Oral Health (NSAOH). METHODS: Data were obtained from the Indigenous Oral Health Literacy Project (IOHLP) based in South Australia. Three sub-populations from the NSAOH were utilised for comparison: National Aboriginal, National non-Aboriginal and South Australian Regional Non-Aboriginal adults. All data were standardised by age group and sex, utilising Census data. RESULTS: Just over 70% of South Australian Regional Aboriginal participants gave a rating of 'excellent, very good or good' for general health, more than 17% lower than each of the other groups. Just over 50% rated their oral health highly, 20% fewer than the proportion for each other group. Stratifying by key socio-demographic factors did not account for all differences. CONCLUSIONS: Proportionally fewer South Australian Regional Aboriginal adults had high ratings of oral and general health than the Aboriginal and non-Aboriginal adults from the national survey, indicating that national-level data might underestimate the proportion of regional Aboriginal Australians with poor oral health.


Asunto(s)
Estado de Salud , Nativos de Hawái y Otras Islas del Pacífico , Salud Bucal , Adulto , Australia/epidemiología , Alfabetización en Salud , Humanos , Australia del Sur/epidemiología
7.
Health Promot Int ; 23(1): 52-9, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18056724

RESUMEN

Indigenous Australians experience poor oral health. Oral health perceptions among a group of rural-dwelling Indigenous Australians were explored so that a culturally appropriate, community-owned oral health promotion initiative might be developed. Focus group methodology was used, with prompt questions including oral health knowledge, oral health's role in general health, how community oral health had changed in recent times, the causes of poor oral health and ways to prevent poor oral health at a community level. Some 34 participants took part; age range 21-72 years. A core category emerged from the data and was labelled 'cultural adaptation'. Five sub-categories were also identified; 'lifestyle changes', 'oral health behaviours', 'barriers to dental care', 'impact of poor oral health' and 'oral health literacy'. Participants felt that historical legacy impacted on the oral health of community members, through continued practices of being told what to do, where to live and what oral health services were available to them. Participants perceived they had little power over their oral health or oral health care decisions. Findings from the focus group discussions were used in the development of a context-specific, oral health promotion initiative, which involved construction of an audiovisual tool in Phase I and a series of interactive, context-specific seminars focused on key issues raised in the focus groups in Phase II. Oral health promotion initiatives among rural-dwelling Indigenous Australians may be more successful if perceptions of the anticipated audience are considered in the design stage of such strategies.


Asunto(s)
Características Culturales , Promoción de la Salud/organización & administración , Nativos de Hawái y Otras Islas del Pacífico , Salud Bucal , Medio Social , Adulto , Factores de Edad , Anciano , Australia , Servicios de Salud Comunitaria/organización & administración , Servicios de Salud Dental/organización & administración , Femenino , Grupos Focales , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Población Rural , Factores Sexuales
8.
Cancer Res ; 55(23): 5540-4, 1995 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-7585630

RESUMEN

The retroviral oncogene qin codes for a protein that belongs to the winged helix family of transcriptional regulators. The Qin protein is localized in the nucleus and binds to the same DNA consensus sequence as rat brain factor 1 (BF-1). Cellular Qin shows greater affinity to DNA than does viral Qin. Alone or fused to the DNA-binding domain of the yeast GAL4 protein, both Qin proteins act as transcriptional repressors. The major transcriptional repression domain maps to the region of amino acids 252-395 of viral Qin.


Asunto(s)
Proteínas Aviares , Proteínas Nucleares/fisiología , Proteínas Oncogénicas , Proteínas Proto-Oncogénicas/fisiología , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción , Transcripción Genética , Proteínas Virales , Secuencia de Aminoácidos , ADN/metabolismo , Proteínas de Unión al ADN , Factores de Transcripción Forkhead , Proteínas Fúngicas/metabolismo , Datos de Secuencia Molecular
9.
Int J Pediatr ; 2012: 496236, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22577401

RESUMEN

Aboriginal Australian children experience profound oral health disparities relative to their non-Aboriginal counterparts. In response to community concerns regarding Aboriginal child oral health in the regional town of Port Augusta, South Australia, a child dental health service was established within a Community Controlled Aboriginal Health Service. A partnership approach was employed with the key aims of (1) quantifying rates of dental service utilisation, (2) identifying factors influencing participation, and (3) planning and establishing a program for delivery of Aboriginal children's dental services that would increase participation and adapt to community needs. In planning the program, levels of participation were quantified and key issues identified through semistructured interviews. After 3.5 years, the participation rate for dental care among the target population increased from 53 to 70 percent. Key areas were identified to encourage further improvements and ensure sustainability in Aboriginal child oral health in this regional location.

10.
Aust Dent J ; 56(3): 272-7, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21884142

RESUMEN

BACKGROUND: There is limited information on self-perceived oral health of homeless populations. This study quantified self-reported oral health among a metropolitan homeless adult population and compared against a representative sample of the metropolitan adult population obtained from the National Survey of Adult Oral Health. METHODS: A total of 248 homeless participants (age range 17-78 years, 79% male) completed a self-report questionnaire. Data for an age-matched, representative sample of metropolitan-dwelling adults were obtained from Australia's second National Survey of Adult Oral Health. Percentage responses and 95% confidence intervals were calculated, with non-overlapping 95% confidence intervals used to identify statistically significant differences between the two groups. RESULTS: Homeless adults reported poorer oral health than their age-matched general population counterparts. Twice as many homeless adults reported visiting a dentist more than a year ago and that their usual reason for dental attendance was for a dental problem. The proportion of homeless adults with a perceived need for fillings or extractions was also twice that of their age-matched general population counterparts. Three times as many homeless adults rated their oral health as 'fair' or 'poor'. CONCLUSIONS: A significantly greater proportion of homeless adults in an Australian metropolitan location reported poorer oral health compared with the general metropolitan adult population.


Asunto(s)
Personas con Mala Vivienda , Salud Bucal , Autoinforme , Población Urbana , Adolescente , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Estudios Transversales , Atención Odontológica/estadística & datos numéricos , Restauración Dental Permanente/estadística & datos numéricos , Dentición , Escolaridad , Etnicidad/estadística & datos numéricos , Femenino , Conductas Relacionadas con la Salud , Humanos , Renta , Masculino , Persona de Mediana Edad , Evaluación de Necesidades/estadística & datos numéricos , Asistencia Pública , Factores Sexuales , Fumar , Australia del Sur , Extracción Dental/estadística & datos numéricos , Adulto Joven
11.
J R Coll Gen Pract ; 30(219): 603-6, 1980 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-6779000

RESUMEN

A survey of the prescribing habits of a group practice of 10,500 patients was conducted during a three-month period to compare the pattern of repeat prescribing with that practised during consultations. Further analysis into therapeutic groups and categories depending on the length of treatment prescribed was performed. The results obtained were compared with annual prescribing rates and it was found that monthly figures could not be accurately extrapolated.


Asunto(s)
Utilización de Medicamentos , Medicina Familiar y Comunitaria , Prescripciones de Medicamentos , Inglaterra , Humanos , Cuidados a Largo Plazo
12.
Cell Growth Differ ; 4(9): 761-8, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8241024

RESUMEN

The Jun protein binds DNA and regulates transcription as a component of the AP-1 transcription factor complex. In its oncogenic form, Jun can transform cells in culture and cause tumors in animals. Both trans-activation and transformation require several functional domains of Jun, including an amino-terminal trans-activation domain. In this study, properties of Jun required for trans-activation and transformation were explored by replacing the trans-activation domains of c-Jun and its oncogenic counterpart, v-Jun, with the constitutively active trans-activation domain from the herpes simplex virus VP16 protein. The VP16-v-Jun chimera retained similar oncogenic properties to its parent, v-Jun. The VP16-c-Jun chimera, however, was considerably more oncogenic than c-Jun. Substitutions of a phenylalanine in the VP16 domain of the VP16-c-Jun chimera diminished or abolished transformation. Each of the chimeras bound to the AP-1 consensus recognition sequence from the collagenase promoter or from the human T-cell leukemia virus type I long terminal repeat in vitro. None of the VP16-Jun chimeras efficiently stimulated transcription from the collagenase promoter or an artificial promoter containing the human T-cell leukemia virus type I element in vivo. These results demonstrate that the Jun trans-activation domain can be replaced by a heterologous trans-activation domain with retention of oncogenic activity. However, this oncogenic activity is not reflected in the trans-activating properties of the chimeras.


Asunto(s)
Proteína Vmw65 de Virus del Herpes Simple/genética , Proteína Oncogénica p65(gag-jun)/genética , Proteínas Recombinantes de Fusión/genética , Simplexvirus , Activación Transcripcional , Animales , Secuencia de Bases , Línea Celular , Embrión de Pollo , Proteínas de Unión al ADN/metabolismo , Datos de Secuencia Molecular
13.
Bioorg Med Chem Lett ; 10(3): 231-4, 2000 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-10698442

RESUMEN

(6R)- and (6S)-6-Fluoro-3-dehydroquinic acids are shown to be substrates for type I and type II dehydroquinases. Their differential reactivity provides insight into details of the reaction mechanism and enables a novel enzyme-substrate imine to be trapped on the type I enzyme.


Asunto(s)
Ácidos Ciclohexanocarboxílicos/metabolismo , Ciclohexanonas/metabolismo , Hidroliasas/metabolismo , Isoenzimas/metabolismo , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Mycobacterium tuberculosis/enzimología , Estereoisomerismo
14.
Nucleic Acids Res ; 26(5): 1240-7, 1998 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-9469832

RESUMEN

Adenovirus DNA polymerase is one of three viral proteins and two cellular proteins required for replication of the adenovirus genome. During initiation of viral DNA synthesis the viral DNA polymerase transfers dCMP onto the adenovirus preterminal protein, to which it is tightly bound. The domain structure of the 140 kDa DNA polymerase has been probed by partial proteolysis and the sites of proteolytic cleavage determined by N-terminal sequencing. At least four domains can be recognised within the DNA polymerase. Adenovirus preterminal protein interacts with three of the four proteolytically derived domains. This was confirmed by cloning and expression of each of the individual domains. These data indicate that, like other members of the pol alpha family of DNA polymerases, the adenovirus DNA polymerase has a multidomain structure and that interaction with preterminal protein takes place with non-contiguous regions of the polypeptide chain over a large surface area of the viral DNA polymerase.


Asunto(s)
Adenoviridae/enzimología , ADN Polimerasa Dirigida por ADN/química , ADN Polimerasa Dirigida por ADN/metabolismo , Fosfoproteínas/metabolismo , Precursores de Proteínas/metabolismo , Proteínas Virales , Adenoviridae/genética , Adenoviridae/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Cartilla de ADN/genética , Replicación del ADN , ADN Polimerasa Dirigida por ADN/genética , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Fosfoproteínas/genética , Precursores de Proteínas/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
15.
Biochemistry ; 40(49): 14821-8, 2001 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-11732901

RESUMEN

3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS, EC 4.1.2.15) catalyzes the condensation of phosphoenolpyruvate (PEP) with erythrose 4-phosphate (E4P) to give DAH7P via an ordered sequential mechanism. In the absence of PEP (the first substrate to bind), E4P binds covalently to the phenylalanine-sensitive DAH7PS of Escherichia coli, DAH7PS(Phe), deactivating the enzyme. Activity is restored on addition of excess PEP but not if deactivation was carried out in the presence of sodium cyanoborohydride. Electrospray mass spectrometry indicates that a single E4P is bound to the protein. These data are consistent with a slow, reversible Schiff base reaction of the aldehydic functionality of E4P with a buried lysine. Molecular modeling indicates that Lys186, a residue at the base of the substrate-binding cavity involved in hydrogen bonding with PEP, is well placed to react with E4P forming an imine linkage that is substantially protected from solvent water.


Asunto(s)
3-Desoxi-7-Fosfoheptulonato Sintasa/metabolismo , Fosfatos de Azúcar/metabolismo , Sitios de Unión , Borohidruros/metabolismo , Indicadores y Reactivos/metabolismo , Modelos Moleculares , Estructura Molecular , Fosfoenolpiruvato/metabolismo , Estructura Terciaria de Proteína , Espectrometría de Masa por Ionización de Electrospray
16.
Mol Genet Genomics ; 270(1): 9-23, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-12884010

RESUMEN

The gene cluster required for paxilline biosynthesis in Penicillium paxilli contains two cytochrome P450 monooxygenase genes, paxP and paxQ. The primary sequences of both proteins are very similar to those of proposed cytochrome P450 monooxygenases from other filamentous fungi, and contain several conserved motifs, including that for a haem-binding site. Alignment of these sequences with mammalian and bacterial P450 enzymes of known 3-D structure predicts that there is also considerable conservation at the level of secondary structure. Deletion of paxP and paxQ results in mutant strains that accumulate paspaline and 13-desoxypaxilline, respectively. These results confirm that paxP and paxQ are essential for paxilline biosynthesis and that paspaline and 13-desoxypaxilline are the most likely substrates for the corresponding enzymes. Chemical complementation of paxilline biosynthesis in paxG (geranygeranyl diphosphate synthase) and paxP, but not paxQ, mutants by the external addition of 13-desoxypaxilline confirms that PaxG and PaxP precede PaxQ, and are functionally part of the same biosynthetic pathway. A pathway for the biosynthesis of paxilline is proposed on the basis of these and earlier results. Electrophysiological experiments demonstrated that 13-desoxypaxilline is a weak inhibitor of mammalian maxi-K channels (Ki=730 nM) compared to paxilline (Ki=30 nM), indicating that the C-13 OH group of paxilline is crucial for the biological activity of this tremorgenic mycotoxin. Paspaline is essentially inactive as a channel blocker, causing only slight inhibition at concentrations up to 1 microM.


Asunto(s)
Sistema Enzimático del Citocromo P-450/genética , Indoles/metabolismo , Indoles/farmacología , Penicillium/enzimología , Canales de Potasio Calcio-Activados/fisiología , Secuencia de Aminoácidos , Animales , Secuencia Conservada , ADN Complementario/genética , Eliminación de Gen , Genes Bacterianos , Prueba de Complementación Genética , Canales de Potasio de Gran Conductancia Activados por el Calcio , Mamíferos , Datos de Secuencia Molecular , Familia de Multigenes , Mutagénesis , Penicillium/genética , Canales de Potasio Calcio-Activados/efectos de los fármacos , Proteínas Recombinantes/efectos de los fármacos , Proteínas Recombinantes/metabolismo , Mapeo Restrictivo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Homología de Secuencia de Aminoácido
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