The Dominant Role of Sp1 in Regulating the Cystathionine β-Synthase –1a and –1b Promoters Facilitates Potential Tissue-specific Regulation by Kruppel-like Factors

Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone and 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol and corticosterone). In mammals, two 11β-hydroxysteroid dehydrogenases (11β-HSD1 and 11β-HSD2) interconvert active and inactive glucocorticoids, allowing tissue-specific regulation of glucocorticoid action. Furthermore, 11β-HSDs are involved in the metabolism of 11-oxy androgens. As zebrafish and other teleost fish lack a direct homologue of 11β-HSD1, we investigated whether they can reduce 11-ketosteroids. We compared glucocorticoid and androgen metabolism between human and zebrafish using recombinant enzymes, microsomal preparations and zebrafish larvae. Our results provide strong evidence for the absence of 11-ketosteroid reduction in zebrafish. Neither human 11β-HSD3 nor the two zebrafish 11β-HSD3 homologues, previously hypothesized to reduce 11-ketosteroids, converted cortisone and 11-ketotestosterone (11KT) to their 11β-hydroxyl forms. Furthermore, zebrafish microsomes were unable to reduce 11-ketosteroids, and exposure of larvae to cortisone or the synthetic analogue prednisone did not affect glucocorticoid-dependent gene expression. Additionally, a dual-role of 11β-HSD2 by inactivating glucocorticoids and generating the main fish androgen 11KT was supported. Thus, due to the lack of 11-ketosteroid reduction, zebrafish and other teleost fish exhibit a limited tissue-specific regulation of glucocorticoid action, and their androgen production pathway is characterized by sustained 11KT production. These findings are of particular significance when using zebrafish as a model to study endocrine functions, stress responses and effects of pharmaceuticals.

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Tissue-specific regulation of the Na, K-ATPase by the cytosolic NaAF: some thoughts on brain function

F1000Research ◽

10.12688/f1000research.2-241.v1 ◽

2013 ◽

Vol 2 ◽

pp. 241 ◽

Cited By ~ 1

Author(s):

Tushar Ray

Keyword(s):

Intracellular Signaling ◽

Local Environment ◽

Ph Homeostasis ◽

Tissue Specific ◽

Dual Channel ◽

Atpase System ◽

Specific Regulation ◽

Histone Kinase ◽

And Function

The dual topology P-2 ATPase, which consists of a α²β² tetramer, explains numerous functions of the cation transporting ATPase system. The ubiquitous cytosolic protein regulator (NaAF) of 170 k Da mass regulates P-2 ATPase function in a low Ca (µM) neighborhood where Ca acts as the terminal regulator in the intracellular signaling cascade. The Na, K- ATPase also seems to function as an H, K-ATPase or a Ca-ATPase in altered states based on the local environment (low pH or high Ca) in a tissue specific manner. These altered effects are analogous to that of the 80 k Da cytosolic HAF in regulating the gastric H, K-ATPase system of the parietal cells. However there are some important differences. The HAF stimulates the Na, K-ATPase but the NaAF cannot stimulate H, K-ATPase. Also, HAF is as effective as NaAF in stimulating the kidney Na, K-ATPase but about 60% as effective in stimulating brain Na, K-ATPase. These observations reveal that the Na, K- ATPase systems from kidney and brain, consisting of different kinds of αβ–isoforms, interact differently with the HAF molecule; thus substantiating that P-2 ATPase system plays different roles in different tissues in response to an universal NaAF. Another rare feature of the HAF is that it has histone kinase activity, suggesting that the HAF and NaAF may be capable of sending a direct signal to the nucleus for gene expression.In this paper, the central role of the NaAF-regulated Na, K-ATPase system in the activity and function of brain tissue is discussed. It is noted that the altered function of the nerve terminus located Na, K-ATPase system works as a Ca-pump (after depolarization) and as a Na-pump (in repolarization) in alternate sequence. The possible role of Ca-sensing receptor (CaR) in the voltage gated channeling of Ca has been raised and the possibility of a dual channel Na/H antiporter (NhaA) in pH homeostasis is discussed.

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Ctcf Haploinsufficiency Mediates Intron Retention in A Tissue-specific Manner

10.1101/851923 ◽

2019 ◽

Author(s):

Adel B Alharbi ◽

Ulf Schmitz ◽

Amy D Marshall ◽

Darya Vanichkina ◽

Rajini Nagarajah ◽

...

Keyword(s):

Gene Expression ◽

Intron Retention ◽

Regulation Of Gene Expression ◽

Splicing Factors ◽

Tissue Specific ◽

Genome Wide ◽

Liver And Kidney ◽

Specific Regulation ◽

Dose Dependent

AbstractCTCF is a master regulator of gene transcription and chromatin organization with occupancy at thousands of DNA target sites. CTCF is essential for embryonic development and somatic cell viability and has been characterized as a haploinsufficient tumor suppressor. Increasing evidence demonstrates CTCF as a key player in several alternative splicing (AS) regulatory mechanisms, including transcription elongation, regulation of splicing factors, and epigenetic regulation. However, the genome-wide impact of Ctcf dosage on AS has not been investigated. We examined the effect of Ctcf haploinsufficiency on gene expression and AS in multiple tissues from Ctcf hemizygous (Ctcf+/-) mice. Distinct tissue-specific differences in gene expression and AS were observed in Ctcf+/- mice compared to wildtype mice. We observed a surprisingly large number of increased intron retention (IR) events in Ctcf+/- liver and kidney, specifically in genes associated with cytoskeletal organization, splicing and metabolism. This study provides further evidence for Ctcf dose-dependent and tissue-specific regulation of gene expression and AS. Our data provide a strong foundation for elucidating the mechanistic role of CTCF in AS regulation and its biological consequences.

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Role of the 5′ untranslated region (UTR) in the tissue-specific regulation of rat tryptophan hydroxylase gene expression by stress

Journal of Neurochemistry ◽

10.1046/j.1471-4159.2002.00989.x ◽

2002 ◽

Vol 82 (3) ◽

pp. 645-654 ◽

Cited By ~ 15

Author(s):

Firas Chamas ◽

Esther L. Sabban

Keyword(s):

Gene Expression ◽

Untranslated Region ◽

Tryptophan Hydroxylase ◽

Tissue Specific ◽

Hydroxylase Gene ◽

Specific Regulation

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Mutation of SlARC6 leads to tissue-specific defects in chloroplast development in tomato

Horticulture Research ◽

10.1038/s41438-021-00567-2 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Jiang Chang ◽

Fanyu Zhang ◽

Haiyang Qin ◽

Peng Liu ◽

Jianfeng Wang ◽

...

Keyword(s):

Chloroplast Development ◽

Spontaneous Mutation ◽

Chloroplast Division ◽

Alternative Mechanism ◽

Wild Type ◽

Mesophyll Cells ◽

Tissue Specific ◽

Dividing Cells ◽

Specific Regulation

AbstractThe proliferation and development of chloroplasts are important for maintaining the normal chloroplast population in plant tissues. Most studies have focused on chloroplast maintenance in leaves. In this study, we identified a spontaneous mutation in a tomato mutant named suffulta (su), in which the stems appeared albinic while the leaves remained normal. Map-based cloning showed that Su encodes a DnaJ heat shock protein that is a homolog of the Arabidopsis gene AtARC6, which is involved in chloroplast division. Knockdown and knockout of SlARC6 in wild-type tomato inhibit chloroplast division, indicating the conserved function of SlARC6. In su mutants, most mesophyll cells contain only one or two giant chloroplasts, while no chloroplasts are visible in 60% of stem cells, resulting in the albinic phenotype. Compared with mature tissues, the meristem of su mutants suggested that chloroplasts could partially divide in meristematic cells, suggesting the existence of an alternative mechanism in those dividing cells. Interestingly, the adaxial petiole cells of su mutants contain more chloroplasts than the abaxial cells. In addition, prolonged lighting can partially rescue the albinic phenotypes in su mutants, implying that light may promote SlACR6-independent chloroplast development. Our results verify the role of SlACR6 in chloroplast division in tomato and uncover the tissue-specific regulation of chloroplast development.

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Chronic Pain: Fundamental Scientific Considerations, Specifically for Legal Claims

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2013.janfeb01 ◽

2013 ◽

Vol 18 (1) ◽

pp. 1-18 ◽

Cited By ~ 1

Author(s):

Robert J. Barth

Keyword(s):

Health Outcomes ◽

Pain Perception ◽

Driving Forces ◽

Psychological Treatment ◽

Dominant Role ◽

Meta Analysis ◽

General Medicine ◽

Pain Syndrome ◽

Problematic Relationship

Abstract Scientific findings have indicated that psychological and social factors are the driving forces behind most chronic benign pain presentations, especially in a claim context, and are relevant to at least three of the AMA Guides publications: AMA Guides to Evaluation of Disease and Injury Causation, AMA Guides to Work Ability and Return to Work, and AMA Guides to the Evaluation of Permanent Impairment. The author reviews and summarizes studies that have identified the dominant role of financial, psychological, and other non–general medicine factors in patients who report low back pain. For example, one meta-analysis found that compensation results in an increase in pain perception and a reduction in the ability to benefit from medical and psychological treatment. Other studies have found a correlation between the level of compensation and health outcomes (greater compensation is associated with worse outcomes), and legal systems that discourage compensation for pain produce better health outcomes. One study found that, among persons with carpal tunnel syndrome, claimants had worse outcomes than nonclaimants despite receiving more treatment; another examined the problematic relationship between complex regional pain syndrome (CRPS) and compensation and found that cases of CRPS are dominated by legal claims, a disparity that highlights the dominant role of compensation. Workers’ compensation claimants are almost never evaluated for personality disorders or mental illness. The article concludes with recommendations that evaluators can consider in individual cases.

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