A possible role of guanine-deaminase inhibitor

1970 ◽  
Vol 26 (2) ◽  
pp. 217-217 ◽  
Author(s):  
S. Kumar
Keyword(s):  
Guanine Deaminase

scholarly journals Upregulated Guanine Deaminase Is Involved in Hyperpigmentation of Seborrheic Keratosis via Uric Acid Release

2021 ◽  
Vol 22 (22) ◽  
pp. 12501
Author(s):  
Kyung Ah Cheong ◽  
In Sup Kil ◽  
Hyuk Wan Ko ◽  
Ai-Young Lee
Keyword(s):  
Uric Acid ◽  
The Elderly ◽  
Epidermal Keratinocytes ◽  
Seborrheic Keratosis ◽  
Human Epidermal Keratinocytes ◽  
Skin Hyperpigmentation ◽  
Guanine Deaminase ◽  
Acid Release ◽  
Skin Specimen

Seborrheic keratosis, which is a benign tumor composed of epidermal keratinocytes, develops common in the elderly. Uric acid generated by upregulated guanine deaminase (GDA) has been identified to cause UV-induced keratinocyte senescence in seborrheic keratosis. Seborrheic keratosis is also frequently pigmented. Growing evidences indicate that hyperuricemia is a risk factor of acanthosis nigricans, an acquired skin hyperpigmentation. The objective of this study was to investigate role of GDA and its metabolic end product, uric acid, in hyperpigmentation of patients with seborrheic keratosis using their lesional and non-lesional skin specimen sets and cultured primary human epidermal keratinocytes with or without GDA overexpression or uric acid treatment. GDA-overexpressing keratinocytes or their conditioned media containing uric acid increased expression levels of MITF and tyrosinase in melanocytes. Uric acid released from keratinocytes was facilitated by ABCG2 transporter with the help of PDZK1 interaction. Released uric acid was taken by URAT1 transporter in melanocytes, stimulating melanogenesis through p38 MAPK activation. Overall, GDA upregulation in seborrheic keratosis plays a role in melanogenesis via its metabolic end product uric acid, suggesting that seborrheic keratosis as an example of hyperpigmentation associated with photoaging.

scholarly journals Guanine Deaminase in Human Epidermal Keratinocytes Contributes to Skin Pigmentation

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2637
Author(s):  
Joon Min Jung ◽  
Tai Kyung Noh ◽  
Soo Youn Jo ◽  
Su Yeon Kim ◽  
Youngsup Song ◽  
...  
Keyword(s):  
Stem Cell Factor ◽  
Small Interfering Rna ◽  
Skin Pigmentation ◽  
Epidermal Keratinocytes ◽  
Melanin Content ◽  
Human Epidermal Keratinocytes ◽  
Guanine Deaminase ◽  
Keratinocyte Culture ◽  
Interfering Rna

Epidermal keratinocytes are considered as the most important neighboring cells that modify melanogenesis. Our previous study used microarray to show that guanine deaminase (GDA) gene expression is highly increased in melasma lesions. Hence, we investigated the role of GDA in skin pigmentation. We examined GDA expression in post-inflammatory hyperpigmentation (PIH) lesions, diagnosed as Riehl’s melanosis. We further investigated the possible role of keratinocyte-derived GDA in melanogenesis by quantitative PCR, immunofluorescence staining, small interfering RNA-based GDA knockdown, and adenovirus-mediated GDA overexpression. We found higher GDA positivity in the hyperpigmentary lesional epidermis than in the perilesional epidermis. Both UVB irradiation and stem cell factor (SCF) plus endothelin-1 (ET-1) were used, which are well-known melanogenic stimuli upregulating GDA expression in both keratinocyte culture alone and keratinocyte and melanocyte coculture. GDA knockdown downregulated melanin content, while GDA overexpression promoted melanogenesis in the coculture. When melanocytes were treated with UVB-exposed keratinocyte-conditioned media, the melanin content was increased. Also, GDA knockdown lowered SCF and ET-1 expression levels in keratinocytes. GDA in epidermal keratinocytes may promote melanogenesis by upregulating SCF and ET-1, suggesting its role in skin hyperpigmentary disorders.

scholarly journals Bacterial Ammeline Metabolism via Guanine Deaminase

2009 ◽  
Vol 192 (4) ◽  
pp. 1106-1112 ◽  
Author(s):  
Jennifer L. Seffernick ◽  
Anthony G. Dodge ◽  
Michael J. Sadowsky ◽  
John A. Bumpus ◽  
Lawrence P. Wackett
Keyword(s):  
Active Sites ◽  
Cyanuric Acid ◽  
Homo Sapiens ◽  
Wild Type ◽  
E Coli ◽  
Guanine Deaminase ◽  
Amidohydrolase Superfamily ◽  
Deamination Reaction

ABSTRACT Melamine toxicity in mammals has been attributed to the blockage of kidney tubules by insoluble complexes of melamine with cyanuric acid or uric acid. Bacteria metabolize melamine via three consecutive deamination reactions to generate cyanuric acid. The second deamination reaction, in which ammeline is the substrate, is common to many bacteria, but the genes and enzymes responsible have not been previously identified. Here, we combined bioinformatics and experimental data to identify guanine deaminase as the enzyme responsible for this biotransformation. The ammeline degradation phenotype was demonstrated in wild-type Escherichia coli and Pseudomonas strains, including E. coli K12 and Pseudomonas putida KT2440. Bioinformatics analysis of these and other genomes led to the hypothesis that the ammeline deaminating enzyme was guanine deaminase. An E. coli guanine deaminase deletion mutant was deficient in ammeline deaminase activity, supporting the role of guanine deaminase in this reaction. Two guanine deaminases from disparate sources (Bradyrhizobium japonicum USDA 110 and Homo sapiens) that had available X-ray structures were purified to homogeneity and shown to catalyze ammeline deamination at rates sufficient to support bacterial growth on ammeline as a sole nitrogen source. In silico models of guanine deaminase active sites showed that ammeline could bind to guanine deaminase in a similar orientation to guanine, with a favorable docking score. Other members of the amidohydrolase superfamily that are not guanine deaminases were assayed in vitro, and none had substantial ammeline deaminase activity. The present study indicated that widespread guanine deaminases have a promiscuous activity allowing them to catalyze a key reaction in the bacterial transformation of melamine to cyanuric acid and potentially contribute to the toxicity of melamine.

Identification of Function and Mechanistic Insights of Guanine Deaminase fromNitrosomonas europaea: Role of the C-Terminal Loop in Catalysis

Biochemistry ◽  
2013 ◽  
Vol 52 (20) ◽  
pp. 3512-3522 ◽  
Author(s):  
Aruna Bitra ◽  
Bhukya Hussain ◽  
Ajay Singh Tanwar ◽  
Ruchi Anand
Keyword(s):  
Guanine Deaminase ◽  
Terminal Loop

Role of dactinomycin in the improved survival of children with Wilms' tumor

JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  
Wilms Tumor

Role of the allergist in diagnosis and management of patients with uveitis

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre
Keyword(s):  
Diagnosis And Management

The power of norms to sway fused group members

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam
Keyword(s):  
Evolutionary Anthropology ◽  
Normative Systems ◽  
Violent Extremism ◽  
Identity Fusion ◽  
Group Members

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.

Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Cognitive Processes ◽  
Evolutionary History ◽  
Behavioral Responses ◽  
History Of ◽  
Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

The role of affect in feelings of obligation

2020 ◽  
Vol 43 ◽  
Author(s):  
Stefen Beeler-Duden ◽  
Meltem Yucel ◽  
Amrisha Vaish
Keyword(s):  
Positive Emotions ◽  
The Creation ◽  
Sense Of Obligation

Abstract Tomasello offers a compelling account of the emergence of humans’ sense of obligation. We suggest that more needs to be said about the role of affect in the creation of obligations. We also argue that positive emotions such as gratitude evolved to encourage individuals to fulfill cooperative obligations without the negative quality that Tomasello proposes is inherent in obligations.

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