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PubMed1988

Nursing education and importance of professional status in the nurse role. Expectations and knowledge of the nurse role.

Development of the nursing profession is an essential goal of nursing education. One way to reach the goal is by clarifying professional status, a status which for the most part is transferred through tacit knowledge. The goals of any nursing education do not include the entire body of tacit knowledge. The development requires recognition of professional status. Over time, significant changes in distribution of nurses' conceptions about professional status are described. The authors contend that conceptions of the importance of professional status are assimilated during work experience. The necessity and importance of role modelling, role repetition and interactions with a professional group are supported by findings from the literature and the authors' current research.

Adult↗

PubMed2004

The effect of organizational conditions (role conflict, role ambiguity, opportunities for professional development, and social support) on job satisfaction and intention to leave among social workers in mental health care.

This study examined the relationships between the organizational conditions of social workers practicing in mental health agencies and their job satisfaction and intention to leave. A sample of 259 social workers, practicing in sixteen mental health agencies in New York State completed a questionnaire that included several measures: role conflict, role ambiguity, social support, extent of opportunities for professional development, type of work activities, job satisfaction and intention to leave. Results showed that the organizational conditions are strong predictors for job satisfaction and intention to leave. The author suggests that it is possible to find an appropriate balance between the professional expectations of social workers and the business-driven aspect of the mental health care environment.

Community Mental Health Centers↗

PubMedDate not supplied

Young Latinas and abortion: the role of cultural factors, reproductive behavior, and alternative roles to motherhood.

Latina women have often been portrayed as holding strong traditional family values leading to a greater propensity for rejection of contraception and abortion. Increasingly, the literature has consistently shown that Latina women use contraception effectively when available; however, much less is known about the prevalence of abortion and the factors related to its use in this population. In this article we examine Latinas' use of abortion and identify factors affecting its use among 1,207 ever-pregnant Latina women age 14-24 recruited at two federally-funded family planning clinics in the Los Angeles metropolitan area. Only a small proportion of the young women in our sample (7.5%) had ever had an induced abortion. In multivariate analysis the variables significantly associated with past abortion included less traditional attitudes about women's roles, higher gravidity, shorter periods of sexual activity, and a higher number of lifetime sexual partners. We conclude that use of abortion among Latinas is driven by role orientation and reproductive variables.

Abortion, Induced↗

PubMed2000

Role tuning between caregiver and care receiver during discharge transition: an illustration of role function mode in Roy's adaptation theory.

The purpose of this study was to develop a conceptual framework to explain the interaction between the caregiver and the care receiver during the discharge transition. Data from face-to-face interviews with 12 care receivers and 16 caregivers were subjected to constant comparative analysis. Findings revealed that role tuning was the process used by caregivers and care receivers to achieve a harmonious pattern of caregiving and care receiving during the transition from hospital to home. This empirical finding can illustrate the concept of role function mode in the Roy adaptation theory and sensitize healthcare providers to the needs of the families during the discharge transition.

Activities of Daily Living↗

PubMed1975

The sick role and the role of the physician reconsidered.

The main substance of this paper was presented orally at a meeting of the Sick Role, organized and chaired by Andrew Twaddle. It was a commentary on four papers and the oral discussion of them. In response to these the paper first discusses the relation of the sick role to deviant behavior and the motivation to become and remain ill. The position was taken that the author never had meant to confine the category of illness to deviant behavior, though its negative valuation should not be forgotten. Nor had he confined it to cases of acute illness, omitting consideration of chronic and other types. The most important issue, however, concerned the structure of the relation between physician and patient. Though insisting that interaction between them is two-way, not one-way, the author insisted that the relation is basically asymmetrical because of the physician's expertise in health matters, gained through training and experience, and his special fiduciary responsibility for the care of the sick. In this respect the relationship is different from others such as the competitive market or the democratic association, but is comparable to the relation of teacher and student in higher education.

Authoritarianism↗

PubMed1989

Nucleus-basal body connector in Chlamydomonas: evidence for a role in basal body segregation and against essential roles in mitosis or in determining cell polarity.

In the unicellular biflagellate green alga Chlamydomonas reinhardtii each basal body is linked to the nucleus by a fibrous nucleus-basal body connector (NBBC) that contains the calcium-binding protein centrin. (Wright et al.: Journal of Cell Biology 101:1903-1912.; Salisbury et al.: Journal of Cell Biology 107:635-642; Huang et al.: Journal of Cell Biology 107:121-131). In order to explore the cellular function of the NBBC we used antiserum directed against centrin to examine a number of mutants known to be defective for basal body assembly and/or localization. Of three variable flagella-number mutants examined, one, vfl-2, is dramatically defective with respect to the NBBC in that 1) the union between basal bodies and nucleus is very labile, 2) there is no detectible centrin in the NBBC region, and 3) total cellular centrin levels are reduced 75-80% relative to wild type. The existence of these defects in a mutant incapable of maintaining normal flagellar number supports the view that the NBBC plays an important role in determining proper basal body localization and/or segregation. In contrast to vfl-2, the mutants vfl-1, vfl-3, uni-1, and bald-2 contain approximately normal levels of centrin and possess stable NBBCs. The observation of NBBCs in the mutant bald-2, which lacks all but very rudimentary basal bodies, indicates that the assembly of the NBBC does not require fully formed basal bodies and that such assembly may not require basal bodies at all. Finally, the possibility that the NBBC is required for induction of gene expression following deflagellation was tested by examining vfl-2 for such induction. Results indicate that the connector does not play a necessary role in the induction process.

Animals↗

PubMed2005

Cadmium-induced malignant transformation in rat liver cells: role of aberrant oncogene expression and minimal role of oxidative stress.

Our study examined the role of oxidative stress and aberrant gene expression in malignant transformation induced by chronic, low-level cadmium exposure in non-tumorigenic rat liver epithelial cell line, TRL 1215. Cells were cultured in 1.0 microM cadmium (as CdCl(2)) for up to 28 weeks and compared to passage-matched control cells. The level of cadmium used for transformation produced no evidence of increased superoxide (O(2) (-*.)) or hydrogen peroxide (H(2)O(2)) levels in the early stages of exposure (</=24 hr). The chronic cadmium exposed liver epithelial cells (CCE-LE) were hyperproliferative with a growth rate about 3-fold higher than control cells. CCE-LE cells produced highly aggressive tumors upon inoculation into mice confirming malignant transformation. Analysis of cellular reactive oxygen species (ROS) showed that CCE-LE cells possessed markedly lower basal levels of intracellular O(2) (-*.)and H(2)O(2) and were very tolerant to high-dose (50 microM) cadmium-induced ROS. Time course studies showed the production of ROS by high-dose cadmium was abolished well in advance of malignant transformation. In contrast, marked overexpression of the oncogenes c-myc and c-jun occurred in transformed CCE-LE cells as evidenced by up to 10-fold increases in both transcript and protein. A significant increase in DNA-binding activity of the transcription factors AP-1 and NF-kappaB occurred in CCE-LE cells. Increases in oncogene expression and transcription factor activity occurred concurrently with malignant transformation. Thus, cadmium-induced ROS occurs as an early, high-dose event but is abolished well in advance of malignant transformation. Low-level chronic cadmium triggers oncogene overexpression possibly by altering critical transcription factor activity. Such changes in cellular gene expression likely culminate in the loss of growth control and cadmium-induced neoplastic transformation in CCE-LE cells, whereas generation of ROS by cadmium seemed to play a minimal role in this transformation.

Animals↗

PubMed1996

Embryonic development of Schwann cells: multiple roles for neuregulins along the pathway.

During the past few years important advances have been realized in the understanding of the molecular and cellular mechanisms operating in the differentiation of Schwann cells from neural crest cells. In particular the development of in vitro culture systems has allowed the analysis of commitment to the Schwann cell lineage, identification of an intermediate between the neural crest cell and the Schwann cell, and initial analysis of the factors controlling determination and differentiation processes. These studies point in particular to major roles for neuregulins which appear to be involved in the control of cell survival, proliferation, and differentiation, as well as of gene expression at different levels of the pathway.

Animals↗

PubMed1999

A Structural Equation Model of the Effects of Negative Affectivity, Leader-Member Exchange, and Perceived Job Mobility on In-role and Extra-role Performance: A Chinese Case.

In this paper, we contrast the effects of leader-member exchange (LMX) with the effects of perceived job mobility on in-role performance and organizational citizenship behavior (OCB). We further model negative affectivity as the antecedent of both LMX and perceived job mobility and suggest that LMX and perceived job mobility mediated the relationship between negative affectivity and performance. We obtained matching data from supervisor and subordinates in a major battery manufacturing company in southern China. Subordinates provided the negative affectivity, perceived job mobility, and LMX assessment, and their immediate supervisors provided the in-role performance and OCB assessment. Results from a structural equation analysis show that both LMX and perceived job mobility predicted OCB. Instead of being a direct antecedent of OCB, the relationship between negative affectivity and OCB is found to be mediated by LMX and perceived job mobility. Theoretical implications of the results are discussed. Copyright 1999 Academic Press.

Journal Article↗

PubMed2003

The role of matrix metalloproteinases (MMPs) in the pathophysiology of chronic obstructive pulmonary disease (COPD): a therapeutic role for inhibitors of MMPs?

Chronic obstructive pulmonary disease (COPD) is the collective term describing two separate chronic lung disease diseases: emphysema and chronic bronchitis (1). Initial clinical symptoms are shortness of breath and occasional cough. As the disease progresses difficulties in breathing becomes more pronounced, the cough more persistent and becomes associated with production of a clear sputum. In severe cases there are additional heart complications. The major risk factor for COPD is cigarette smoking. Between 1980 and 1990 there was a 22% increase in the occurrence of the disease with attributed 84,000 deaths in 1990 in the USA (www.nhlbi.nih.gov/health). Current therapies address the symptoms and range from bronchodilators, corticosteroids to oxygen. While there are no effective cures, although the disease can be prevented and progress slowed in many cases by removing the principal risk factor: cigarette smoking. Progression of the disease is associated with degradation of elastin in the walls of the alveoli, resulting in the functional destruction of the these organs. The net increase in proteolytic activity leading to this loss of alveoli function is a growing focus of pharmaceutical efforts for identification of a therapy for the amelioration of this disease. Of specific interest for this review has been the potential roles of members of the MMP family in both the destruction of elastin and the aberrant remodeling of damaged alveoli. An example of such a MMP is Metalloelastase. Metalloelastase (MMP-12) is (as the name suggests) capable of degrading elastin, as well as other extra-cellular matrix components. It is produced predominantly by infiltrating macrophages and appears essential for macrophage migration through extra-cellular matrix (2). Mouse metalloelastase knock-out studies implicate this enzyme as a key mediator in the pathology associated with cigarette smoke induced emhysema (3). There is also associative evidence from human genetic and animal studies suggesting a pathological link with other MMPs, such as MMPs 1,2,3,8 & 9. The evidence for the role of these MMPs in the pathological processes associated with COPD and prospects for MMP inhibitors as the basis for future therapies will be addressed in this review.

Animals↗

PubMed2002

Arachidonic acid-derived bioactive lipids: their role and the role for their inhibitors in dermatology.

BACKGROUND: In addition to corticosteroids, there are increasing numbers of anti-inflammatory agents that specifically target bioactive lipids generated from arachidonic acid. Knowledge of the diverse mechanisms of action of these different bioactive lipids holds promise in the therapy of a wide spectrum of cutaneous and systemic disorders. OBJECTIVE: Therapeutic manipulations of these lipid molecules through inhibition, stimulation, or direct replacement have broad physiologic effects. These therapeutic strategies not only modulate inflammation, pain, and hemostatic parameters, they also play a role in cardiac, respiratory, renal, and gastrointestinal function and disease, as well as in angiogenesis and in factors that control cell growth and apoptosis important in carcinogenesis. CONCLUSION: Newer drug discovery methods, including combinatorial chemistry with molecular modeling, have made it possible to develop inhibitors and analogs with increasing specificity and bioactivity and decreasing toxicity. Although the application of these analogs and inhibitors for cutaneous disease is limited today, either as primary agents or adjuvant therapy, these drugs will have a place in our therapeutic regimes of the future. We present a review of the therapeutic agents now available from manipulation of these bioactive lipids, and their role and future in dermatology.

Anti-Inflammatory Agents↗

PubMed1976

Catecholamines and self-stimulation: evidence suggesting a reinforcing role for noradrenaline and a motivating role for dopamine.

Investigation of the role of noradrenaline (NA) and dopamine (DA) in self-stimulation showed that d-amphetamine (which releases more DA than does l-amphetamine, but not more NA) was much more effective than l-amphetamine in enhancing self-stimulation of NA sites in the locus coeruleus and near-lateral hypothalamus. In DA sites in the substantia nigra and far-lateral hypothalamus the effects of the 2 isomers were confirmed to be more nearly equal. Thymoxamine HCl (10 mg/kg IP), a specific alpha-adrenergic receptor blocker, depressed self-stimulation at all sites, but significantly more severely at DA sites. Thus the drugs most effective in influencing self-stimulation at a particular site were those acting predominantly on the unstimulated system. These findings were interpreted in terms of a hypothesis that DA and NA play complementary roles in self-stimulation and that both are essential; or, more specifically, that DA pathways, implicated in other motivational activites, contribute to a state of drive or arousal necessary for self-stimulation; while response-contingent noradrenergic activity (elicited by the electrodes directly via a transsynaptic route) mediates reinforcement. Further predictions from this hypothesis were tested as follows: (1) Direct pharmacological stimulants of adrenergic alpha-receptors should disrupt self-stimulation by acting randomly on the reinforcement system and disrupting response-reward contingencies; this was confirmed by the finding that the alpha-receptor stimulant clonidine HCl (0.05 mg/kg) depressed self-stimulation at all sites tested. (2) Drect stimulants of DA receptors should enhance self-stimulation of NA sites by augmenting dopaminergic motivational activity; but in rats with DA electrodes, noncontingent stimulation of DA receptors would also impose similar noncontingent activity on the transsynaptic noradrenergic reinforcement pathways and thus depress self-stimulation; this was confirmed by the finding that apomorphine (0.3-1.0 mg/kg) was strongly stimulant for NA electrodes but strongly depressant for DA electrodes, and that the degree and direction of these effects was highly correlated with the differential effects of d- l-amphetamine (rho = .65, p less than 0.01). Neither effect of apomorphine depended on the occurrence of motor stereotypy. These results can be interpreted in terms of 2-component models for self-stimulation, with the predominant transmitter of the drive component being identified as DA and that g the reinforcing component as NA.

Amphetamine↗

PubMed1997

Differential roles of myocardial Ca2+ channels and Na+/Ca2+ exchange in myocardial reperfusion injury in open chest dogs: relative roles during ischemia and reperfusion.

OBJECTIVE: Compare the roles of Ca2+ channels and Na+/Ca2+ exchange in reperfusion injury (reperfusion ventricular fibrillation and myocardial stunning). METHODS: Open chest dogs undergoing 15 minutes of left anterior descending coronary artery occlusion and 3 hours of reperfusion were randomized to controls or intracoronary infusions of the respective antagonists, nifedipine (50 micrograms/min) or amiloride (5 mg/min), according to five protocols: (A) 40 minutes before occlusion to 30 minutes after reperfusion; (B) 2 minutes before to 5 minutes after reperfusion; (C) 10 minutes before to 10 minutes after reperfusion (two step infusion for nifedipine only 5 micrograms/min during occlusion and 50 micrograms/min after reperfusion); and (D) 0 to 30 minutes after reperfusion. The role of Ca2+ channels was further investigated by infusing the agonist, Bay K 8644 (50 micrograms/min), alone or simultaneously with any protocol B, C, or D infusions altering both reperfusion ventricular fibrillation and myocardial stunning. RESULTS: Effects of the agents on injury did not result from hemodynamic effects or alterations in blood flow. Amiloride had no effect on ventricular fibrillation. Only protocol A infusion of amiloride prevented myocardial stunning. In contrast, protocol A and B infusions of nifedipine prevented both myocardial stunning (p = ns vs. baseline, p < 0.01 vs. control) and ventricular fibrillation (0%, p < 0.01). Protocol C prevented reperfusion ventricular fibrillation, but not stunning (p = ns vs. control). Protocol D did not alter injury. Bay K 8644 co-treatment reversed the effects of Protocol B infusion of nifedipine. Ventricular fibrillation was common and postischemic function worst in dogs treated with Bay K 8644 alone (protocol B). CONCLUSION: Myocardial Ca2+ channels contribute to both reperfusion ventricular fibrillation and stunning, whereas Na+/Ca2+ exchange contributes only to stunning. Inhibitors of myocardial Ca2+ channels are protective when infused in high doses just before reperfusion, whereas the efficacy of Na+/Ca2+ exchange inhibitors is dependent on pretreatment.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1985

Defining the physiologic and pathophysiologic roles of renin: the role of specific inhibitors.

Although renin was identified as playing a role in cardiovascular homeostasis by the experiments of Goldblatt in the 1930's, neither its physiologic role in organs other than the kidney nor its contribution to the genesis of essential hypertension has been defined as yet. It is difficult to interpret studies with converting enzyme inhibitors because of their multiple pharmacologic effects. Specific inhibitors of renin appropriate for clinical investigation would help resolve many questions. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogs of angiotensinogens, and peptides that are related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogs will be the first applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Recently, remarkably active compounds have been synthesized by reducing the peptide bond that is cleaved by renin, or by incorporating the amino acid statine, found in pepstatin. These compounds have been shown now to be effective in dogs, rats, and monkeys, and most recently, preliminary studies have reported their efficacy in humans. Recent studies with one of these inhibitors, RIP, raise questions concerning both its specificity and site of action.

Angiotensinogen↗

PubMed2003

Role of central cholinergic receptor sub-types in spatial working memory: a five-arm maze task in mice provides evidence for a functional role of nicotinic receptors in mediating trace access processes.

A delayed-matching spatial working memory protocol in a 5-arm maze was used to test the hypothesis of differential roles for central nicotinic and muscarinic cholinergic receptors in mediating task performance. In experiment 1, using a within subjects-repeated design, groups of C57Bl/6 mice, previously trained to criterion with a 4 h retention interval separating presentation and test phases, received i.p. injections of either saline, scopolamine (0.8 mg/kg), mecamylamine (8.0 mg/kg), or the combination of scopolamine and mecamylamine before re-testing. Injections were given either, a) 15 min pre-presentation or, b) 30 s, c) 15 min, d) 3 h 45 min post-presentation in order to differentially affect the acquisition, trace maintenance and recall phases. Significant decreases in correct responses were observed for each drug treatment but the effects were a function of the time of treatment. Results of condition d), (i.e.15 min before retention test) confirm previous reports of severe disruption by each antagonist and their combination on retention. However, conditions a-c) show a constant disruption by scopolamine, increasing disruption by mecamylamine, whereas the combined treatment was without effect. Although the data show that central nicotinic and muscarinic antagonists both modulate working memory performance, they indicate first, that scopolamine-induced "amnesia" results, not from selective post-synaptic M1 muscarinic blockade but from indirect over-activation of nicotinic receptors. Second, the observation of high levels of retention although nicotinic and muscarinic receptors had undergone combined blockade during a large part of the retention interval is incompatible with the concept that test-induced activation of central cholinergic neurones mediates memory trace maintenance. Finally, taken with data from experiment 2, using a short (20 min) treatment-to-test interval, we conclude that central nicotinic receptors play a key role in attentional processes enabling working memory trace access during retrieval.

Animals↗

PubMed2000

Role for cysteinyl leukotriene receptor antagonist therapy in asthma and their potential role in allergic rhinitis based on the concept of "one linked airway disease".

OBJECTIVE: This review focuses on the shared pathophysiology of asthma and allergic rhinitis. The similarities illustrate the "one linked airway disease" concept, a unifying theory of these upper and lower airway inflammatory disorders. Since leukotrienes are mediators in both conditions, studies have been performed to assess the potential therapeutic role of cysteinyl leukotriene antagonists. The purpose of this paper is to provide an overview of the accumulating data concerning these agents in treating asthma and allergic rhinitis. DATA SOURCES: Relevant publications obtained from a literature review. STUDY SELECTION: Relevant publications on the topics of leukotrienes, leukotriene receptor antagonists, asthma, and allergic rhinitis were critically evaluated. RESULTS AND CONCLUSIONS: Studies to date have documented the efficacy of cysteinyl leukotriene receptor antagonists for asthma. The pathophysiology of allergic rhinitis and its similarities to asthma suggest that these agents could play a significant therapeutic role in managing this upper airway disorder. Because the leukotriene antagonists are oral agents, they may be valuable in treating not only either condition but also both at the same time when they coexist. They appear to be beneficial when prescribed as the initial medicine and when used in conjunction with other therapies.

Asthma↗

PubMed2005

Aspartate 120 of Escherichia coli methylenetetrahydrofolate reductase: evidence for major roles in folate binding and catalysis and a minor role in flavin reactivity.

Escherichia coli methylenetetrahydrofolate reductase (MTHFR) catalyzes the NADH-linked reduction of 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate) to 5-methyltetrahydrofolate (CH(3)-H(4)folate) using flavin adenine dinucleotide (FAD) as cofactor. MTHFR is unusual among flavin oxidoreductases because it contains a conserved, negatively rather than positively charged amino acid (aspartate 120) near the N1-C2=O position of the flavin. At this location, Asp 120 is expected to influence the redox properties of the enzyme-bound FAD. Modeling of the CH(3)-H(4)folate product into the enzyme active site suggests that Asp 120 may also play crucial roles in folate binding and catalysis. We have replaced Asp 120 with Asn, Ser, Ala, Val, and Lys and have characterized the mutant enzymes. Consistent with a loss of negative charge near the flavin, the midpoint potentials of the mutants increased from 17 to 30 mV. A small kinetic effect on the NADH reductive half-reaction was also observed as the mutants exhibited a 1.2-1.5-fold faster reduction rate than the wild-type enzyme. Catalytic efficiency (k(cat)/K(m)) in the CH(2)-H(4)folate oxidative half-reaction was decreased significantly (up to 70000-fold) and in a manner generally consistent with the negative charge density of position 120, supporting a major role for Asp 120 in electrostatic stabilization of the putative 5-iminium cation intermediate during catalysis. Asp 120 is also intimately involved in folate binding as increases in the apparent K(d) of up to 15-fold were obtained for the mutants. Examining the E(red) + CH(2)-H(4)folate reaction at 4 degrees C, we obtained, for the first time, evidence for the rapid formation of a reduced enzyme-folate complex with wild-type MTHFR. The more active Asp120Ala mutant, but not the severely impaired Asp120Lys mutant, demonstrated the species, suggesting a connection between the extent of complex formation and catalytic efficiency.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗

PubMed2006

Competing roles of aldo-keto reductase 1A1 and cytochrome P4501B1 in benzo[a]pyrene-7,8-diol activation in human bronchoalveolar H358 cells: role of AKRs in P4501B1 induction.

Benzo[a]pyrene (BP) requires metabolic activation to electrophiles to exert its deleterious effects. We compared the respective roles of aldo-keto reductase 1A1 (AKR1A1, aldehyde reductase) and P4501B1 in the formation of BP-7,8-dione and BP-tetrols, respectively, in intact bronchoalveolar cells manipulated to express either enzyme. Metabolite formation was confirmed by HPLC/MS and quantitatively measured by HPLC/UV/beta-RAM. In TCDD-treated H358 cells (P4501B1 expression), the anti-BPDE hydrolysis product BP-tetrol-1 increased over 3-12 h to a constant level. In H358 AKR1A1 transfectants, formation of BP-7,8-dione was elevated for 3-12 h but significantly decreased after 24 h. Interestingly, BP-tetrols were also detected in AKR1A1 transfectants even though they do not constitutively express P4501A1/P4501B1 enzymes. Northern and Western blotting confirmed the induction of P4501B1 by BP-7,8-dione in parental cells and the induction of P4501B1 by BP-7,8-diol in AKR1A1-transfected cells. P4501B1 induction was blocked in AKR1A1 transfectants by the AKR1A1 inhibitor (sulfonylnitromethane), the o-quinone scavenger (N-acetyl-l-cysteine), or the cytosolic AhR antagonist (diflubenzuron). Attenuation of P4501B1 induction in these cells was verified by measuring a decrease in BP-tetrol formation. Our studies show that the formation of BP-7,8-dione by AKR1A1 in human bronchoalveolar cells leads to an induction of P4501B1 and that a functional consequence of this induction is elevated anti-BPDE production as detected by increased BP-tetrol formation. Therefore, the role of AKR1A1 in the activation of BP-7,8-diol is bifunctional; that is, it directly activates BP-7,8-diol to the reactive and redox-active PAH o-quinone (BP-7,8-dione) and it indirectly trans-activates the P4501B1 gene by generating the aryl hydrocarbon receptor (AhR) ligand BP-7,8-dione.

Alcohol Oxidoreductases↗