scholarly journals Knockout of the hsd11b2 Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults

2021 ◽  
Vol 22 (22) ◽  
pp. 12525
Author(s):  
Antonia Theodoridi ◽  
Alberto Dinarello ◽  
Lorenzo Badenetti ◽  
Michail A. Pavlidis ◽  
Luisa Dalla Valle ◽  
...  
Keyword(s):  
Stress Response ◽  
Adult Males ◽  
Wild Type ◽  
Good Tool ◽  
Zebrafish Model ◽  
Basal Cortisol ◽  
Inactive Form ◽  
Old Adult ◽  
Cortisol Levels ◽  
One Year

The Hsd11b2 enzyme converts cortisol into its inactive form, cortisone and regulates cortisol levels, in particular in response to stress. Taking advantage of CRISPR/Cas9 technology, we generated a hsd11b2 zebrafish mutant line to evaluate the involvement of this gene in stress response regulation. The absence of a functional Hsd11b2 affects survival of zebrafish, although homozygous hsd11b2−/− mutants can reach adulthood. Reproductive capability of hsd11b2−/− homozygous adult males is almost completely abrogated, while that of females is reduced. Interestingly, basal cortisol levels and glucocorticoid-dependent transcriptional activities are not affected by the mutation. In agreement with basal cortisol results, we also demonstrated that basal response to light (LMR-L/D) or mechanical (VSRA) stimuli is not significantly different in wild-type (hsd11b2+/+) compared to mutant larvae. However, after exposure to an acute stressor, the cortisol temporal patterns of synthesis and release are prolonged in both 5 days post fertilization larvae and one-year-old adult hsd11b2−/− zebrafish compared to wild-type siblings, showing at the same time, at 5 dpf, a higher magnitude in the stress response at 10 min post stress. All in all, this new zebrafish model represents a good tool for studying response to different stressors and to identify mechanisms that are induced by cortisol during stress response.

Prenatal betamethasone exposure results in pituitary-adrenal hyporesponsiveness in adult sheep

2007 ◽  
Vol 292 (1) ◽  
pp. E61-E70 ◽  
Author(s):  
Deborah M. Sloboda ◽  
Timothy J. M. Moss ◽  
Shaofu Li ◽  
Dorota Doherty ◽  
Ilias Nitsos ◽  
...  
Keyword(s):  
Mrna Levels ◽  
Fetal Exposure ◽  
Rt Pcr ◽  
Basal Cortisol ◽  
Acth Receptor ◽  
Cortisol Levels ◽  
Glucocorticoid Receptor Mrna ◽  
One Year ◽  
Synthetic Glucocorticoids ◽  
Cytochrome P 450

Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hypothalamic-pituitary-adrenal (HPA) activity persisting to one year of age. We aimed to determine the effects of single or repeated maternal or fetal betamethasone injections on offspring HPA activity at 2 and 3 yr of age and whether changes in adrenal mediators of steroidogenesis contribute to changes in pituitary-adrenal function. Pregnant ewes or their fetuses received either repeated intramuscular saline or betamethasone injections (0.5 mg/kg) at 104, 111, 118, and 124 days of gestation (dG) or a single betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG. Offspring were catheterized at 2 and 3 yr of age and given corticotrophin-releasing hormone + arginine vasopressin challenges. Adrenal tissue was collected for quantitative RT-PCR mRNA determination at 3.5 yr of age. In 2-yr-old offspring, maternal betamethasone injections did not alter basal ACTH or cortisol levels, but repeated injections elevated ACTH responses. At 3 yr of age, basal ACTH was elevated, and both basal and stimulated cortisol levels were suppressed by repeated maternal injections. Basal and stimulated cortisol-to-ACTH ratios and basal cortisol-to-cytochrome P-450 17α-hydroxylase (P450c17) mRNA ratios were suppressed by repeated injections. Repeated fetal betamethasone injections attenuated basal ACTH and cortisol levels in offspring at 2 but not 3 yr of age. Plasma changes were not associated with altered adrenal P450c17, ACTH receptor, β-hydroxysteroid dehydrogenase, or glucocorticoid receptor mRNA levels. These data suggest that maternal, but not fetal, betamethasone administration results in adrenal suppression in adulthood.

scholarly journals NMR and LC-MS-Based Metabolomics to Study Osmotic Stress in Lignan-Deficient Flax

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 767
Author(s):  
Kamar Hamade ◽  
Ophélie Fliniaux ◽  
Jean-Xavier Fontaine ◽  
Roland Molinié ◽  
Elvis Otogo Nnang ◽  
...  
Keyword(s):  
Stress Response ◽  
Osmotic Stress ◽  
Biosynthetic Pathway ◽  
Potential Role ◽  
Plant Secondary Metabolites ◽  
Wild Type ◽  
Osmotic Stress Response ◽  
Transgenic Flax ◽  
Insight Into

Lignans, phenolic plant secondary metabolites, are derived from the phenylpropanoid biosynthetic pathway. Although, being investigated for their health benefits in terms of antioxidant, antitumor, anti-inflammatory and antiviral properties, the role of these molecules in plants remains incompletely elucidated; a potential role in stress response mechanisms has been, however, proposed. In this study, a non-targeted metabolomic analysis of the roots, stems, and leaves of wild-type and PLR1-RNAi transgenic flax, devoid of (+) secoisolariciresinol diglucoside ((+) SDG)—the main flaxseed lignan, was performed using 1H-NMR and LC-MS, in order to obtain further insight into the involvement of lignan in the response of plant to osmotic stress. Results showed that wild-type and lignan-deficient flax plants have different metabolic responses after being exposed to osmotic stress conditions, but they both showed the capacity to induce an adaptive response to osmotic stress. These findings suggest the indirect involvement of lignans in osmotic stress response.

scholarly journals Overexpression of the pitaya phosphoethanolamine N-methyltransferase gene (HpPEAMT) enhanced simulated drought stress in tobacco

2021 ◽  
Author(s):  
Ai-Hua Wang ◽  
Lan Yang ◽  
Xin-Zhuan Yao ◽  
Xiao-Peng Wen
Keyword(s):  
Drought Stress ◽  
Stress Response ◽  
Transgenic Plants ◽  
Drought Tolerance ◽  
Transgenic Tobacco ◽  
Sequence Similarity ◽  
Amino Acid Sequence Similarity ◽  
Transgenic Tobacco Plants ◽  
Wild Type ◽  
Tobacco Plants

AbstractPhosphoethanolamine N-methyltransferase (PEAMTase) catalyzes the methylation of phosphoethanolamine to produce phosphocholine and plays an important role in the abiotic stress response. Although the PEAMT genes has been isolated from many species other than pitaya, its role in the drought stress response has not yet been fully elucidated. In the present study, we isolated a 1485 bp cDNA fragment of HpPEAMT from pitaya (Hylocereus polyrhizus). Phylogenetic analysis showed that, during its evolution, HpPEAMT has shown a high degree of amino acid sequence similarity with the orthologous genes in Chenopodiaceae species. To further investigate the function of HpPEAMT, we generated transgenic tobacco plants overexpressing HpPEAMT, and the transgenic plants accumulated significantly more glycine betaine (GB) than did the wild type (WT). Drought tolerance trials indicated that, compared with those of the wild-type (WT) plants, the roots of the transgenic plants showed higher drought tolerance ability and exhibited improved drought tolerance. Further analysis revealed that overexpression of HpPEAM in Nicotiana tabacum resulted in upregulation of transcript levels of GB biosynthesis-related genes (NiBADH, NiCMO and NiSDC) in the leaves. Furthermore, compared with the wild-type plants, the transgenic tobacco plants displayed a significantly lower malondialdehyde (MDA) accumulation and higher activities of the superoxide dismutase (SOD) and peroxidase (POD) antioxidant enzymes under drought stress. Taken together, our results suggested that HpPEAMT enhanced the drought tolerance of transgenic tobacco.

scholarly journals RpoS-Dependent Stress Response and Exoenzyme Production in Vibrio vulnificus

2003 ◽  
Vol 69 (10) ◽  
pp. 6114-6120 ◽  
Author(s):  
A. Hülsmann ◽  
T. M. Rosche ◽  
I.-S. Kong ◽  
H. M. Hassan ◽  
D. M. Beam ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Stress Response ◽  
Mutant Strain ◽  
Environmental Changes ◽  
Vibrio Vulnificus ◽  
High Sensitivity ◽  
Striking Difference ◽  
Wild Type ◽  
Hydrolytic Activities ◽  
In The Wild

ABSTRACT Vibrio vulnificus is an estuarine bacterium capable of causing rapidly fatal infections through both ingestion and wound infection. Like other opportunistic pathogens, V. vulnificus must adapt to potentially stressful environmental changes while living freely in seawater, upon colonization of the oyster gut, and upon infection of such diverse hosts as humans and eels. In order to begin to understand the ability of V. vulnificus to respond to such stresses, we examined the role of the alternate sigma factor RpoS, which is important in stress response and virulence in many pathogens. An rpoS mutant of V. vulnificus strain C7184o was constructed by homologous recombination. The mutant strain exhibited a decreased ability to survive diverse environmental stresses, including exposure to hydrogen peroxide, hyperosmolarity, and acidic conditions. The most striking difference was a high sensitivity of the mutant to hydrogen peroxide. Albuminase, caseinase, and elastase activity were detected in the wild type but not in the mutant strain, and an additional two hydrolytic activities (collagenase and gelatinase) were reduced in the mutant strain compared to the wild type. Additionally, the motility of the rpoS mutant was severely diminished. Overall, these studies suggest that rpoS in V. vulnificus is important for adaptation to environmental changes and may have a role in virulence.

scholarly journals Impaired Temperature Stress Response of a Streptococcus thermophilus deoD Mutant

2003 ◽  
Vol 69 (2) ◽  
pp. 1287-1289 ◽  
Author(s):  
Mario Varcamonti ◽  
Maria R. Graziano ◽  
Romilde Pezzopane ◽  
Gino Naclerio ◽  
Slavica Arsenijevic ◽  
...  
Keyword(s):  
Growth Rate ◽  
Stress Response ◽  
Heat Shock ◽  
Temperature Stress ◽  
Streptococcus Thermophilus ◽  
Wild Type ◽  
Temperature Shock ◽  
Dual Response ◽  
Survival Capacity

ABSTRACT An insertional deoD mutant of Streptococcus thermophilus strain SFi39 had a reduced growth rate at 20°C and an enhanced survival capacity to heat shock compared to the wild type, indicating that the deoD product is involved in temperature shock adaptation. We report evidence that ppGpp is implicated in this dual response.

scholarly journals 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response

2012 ◽  
Vol 302 (6) ◽  
pp. E654-E665 ◽  
Author(s):  
Banumathi K. Cole ◽  
Norine S. Kuhn ◽  
Shamina M. Green-Mitchell ◽  
Kendall A. Leone ◽  
Rebekah M. Raab ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Stress Response ◽  
Er Stress ◽  
Pancreatic Islets ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Stress Markers ◽  
Deficient Mice

Central obesity is associated with chronic inflammation, insulin resistance, β-cell dysfunction, and endoplasmic reticulum (ER) stress. The 12/15-lipoxygenase enzyme (12/15-LO) promotes inflammation and insulin resistance in adipose and peripheral tissues. Given that obesity is associated with ER stress and 12/15-LO is expressed in adipose tissue, we determined whether 12/15-LO could mediate ER stress signals. Addition of 12/15-LO lipid products 12(S)-HETE and 12(S)-HPETE to differentiated 3T3-L1 adipocytes induced expression and activation of ER stress markers, including BiP, XBP-1, p-PERK, and p-IRE1α. The ER stress inducer, tunicamycin, upregulated ER stress markers in adipocytes with concomitant 12/15-LO activation. Addition of a 12/15-LO inhibitor, CDC, to tunicamycin-treated adipocytes attenuated the ER stress response. Furthermore, 12/15-LO-deficient adipocytes exhibited significantly decreased tunicamycin-induced ER stress. 12/15-LO action involves upregulation of interleukin-12 (IL-12) expression. Tunicamycin significantly upregulated IL-12p40 expression in adipocytes, and IL-12 addition increased ER stress gene expression; conversely, LSF, an IL-12 signaling inhibitor, and an IL-12p40-neutralizing antibody attenuated tunicamycin-induced ER stress. Isolated adipocytes and liver from 12/15-LO-deficient mice fed a high-fat diet revealed a decrease in spliced XBP-1 expression compared with wild-type C57BL/6 mice on a high-fat diet. Furthermore, pancreatic islets from 12/15-LO-deficient mice showed reduced high-fat diet-induced ER stress genes compared with wild-type mice. These data suggest that 12/15-LO activity participates in ER stress in adipocytes, pancreatic islets, and liver. Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity.

Cytokine Inhibition after Glucocorticoid Exposure in Healthy Men with Low versus High Basal Cortisol Levels

2009 ◽  
Vol 16 (4) ◽  
pp. 245-250 ◽  
Author(s):  
Mats Lekander ◽  
Jennie Axén ◽  
Urban Knutsson ◽  
Caroline Olgart Höglund ◽  
Sigbritt Werner ◽  
...  
Keyword(s):  
Healthy Men ◽  
Cytokine Inhibition ◽  
Basal Cortisol ◽  
Cortisol Levels

Abstract 292: The Role of the ATF6 Branch of the ER Stress Response in the Endocrine Heart

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Erik A Blackwood ◽  
Christopher C Glembotski
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Proteolytic Cleavage ◽  
Isolated Perfused Heart ◽  
Wild Type ◽  
Atrial Myocytes ◽  
Perfused Heart ◽  
Er Stress Response

Rationale: Atrial natriuretic peptide (ANP) is stored in the heart in large dense core granules of atrial myocytes as a biologically inactive precursor, pro-ANP. Hemodynamic stress and atrial stretch stimulate coordinate secretion and proteolytic cleavage of pro-ANP to its bioactive form, ANP, which promotes renal salt excretion and vasodilation, which, together contribute to decreasing blood pressure. While the ATF6 branch of the ER stress response has been studied in ventricular tissue mouse models of myocardial ischemia and pathological hypertrophy, roles for ATF6 and ER stress on the endocrine function of atrial myocytes have not been studied. Objective/Methods: To address this gap in our knowledge, we knocked down ATF6 in primary cultured neonatal rat atrial myocytes (NRAMs) using a chemical inhibitor of the proteolytic cleavage site enabling ATF6 activation and siRNA and measured ANP expression and secretion basally and in response to alpha- adrenergic agonist stimulation using phenylephrine. We also compared the ANP secretion from wild- type mice and ATF6 knockout mice in an ex vivo Langendorff model of the isolated perfused heart. Results: ATF6 knockdown in NRAMs significantly impaired basal and phenylephrine-stimulated ANP secretion. ATF6 knockout mice displayed lower levels of ANP in atrial tissue at baseline as well as after phenylephrine treatment. Similarly, in the ex vivo isolated perfused heart model, less ANP was detected in effluent of ATF6 knockout hearts compared to wild-type hearts. Conclusions: The ATF6 branch of the ER stress response is necessary for efficient co-secretional processing of pro-ANP to ANP and for agonist-stimulated ANP secretion from atrial myocytes. As ANP is secreted in a regulated manner in response to a stimulus and pro-ANP is synthesized and packaged through the classical secretory pathway, we posit that ATF6 is required for adequate expression, folding, trafficking, processing and secretion of biologically active ANP from the endocrine heart.

scholarly journals Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio

2018 ◽  
Vol 115 (52) ◽  
pp. E12435-E12442 ◽  
Author(s):  
Marilyn N. Vera-Chang ◽  
Antony D. St-Jacques ◽  
Rémi Gagné ◽  
Chris J. Martyniuk ◽  
Carole L. Yauk ◽  
...  
Keyword(s):  
Adult Males ◽  
Therapeutic Drugs ◽  
Stage Of Development ◽  
Prevalence Of Depression ◽  
Prescription Rates ◽  
Interrenal Cells ◽  
Cortisol Levels ◽  
Negative Impacts ◽  
Low Cortisol

The global prevalence of depression is high during childbearing. Due to the associated risks to the mother and baby, the selective serotonin reuptake inhibitor fluoxetine (FLX) is often the first line of treatment. Given that FLX readily crosses the placenta, a fetus may be susceptible to the disruptive effects of FLX during this highly plastic stage of development. Here, we demonstrate that a 6-day FLX exposure to a fetus-relevant concentration at a critical developmental stage suppresses cortisol levels in the adult zebrafish (F0). This effect persists for three consecutive generations in the unexposed descendants (F1 to F3) without diminution and is more pronounced in males. We also show that the in vivo cortisol response of the interrenal (fish “adrenal”) to an i.p. injection of adrenocorticotropic hormone was also reduced in the males from the F0 and F3 FLX lineages. Transcriptomic profiling of the whole kidney containing the interrenal cells revealed that early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F0 and F3 generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F0 to F2 FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs.

scholarly journals Basal cortisol levels and the relationship with clinical symptoms in multiple sclerosis: a systematic review

2018 ◽  
Vol 76 (9) ◽  
pp. 622-634 ◽  
Author(s):  
Gabriela Magalhães Pereira ◽  
Nayron Medeiros Soares ◽  
Andreo Rysdyk de Souza ◽  
Jefferson Becker ◽  
Alessandro Finkelsztejn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Neurodegenerative Disease ◽  
Web Of Science ◽  
Clinical Symptoms ◽  
Depression And Anxiety ◽  
Basal Cortisol ◽  
Cortisol Levels ◽  
The Relationship ◽  
Pituitary Adrenal Axis

ABSTRACT Multiple sclerosis (MS) is a demyelinating, progressive and neurodegenerative disease. A disturbance on the hypothalamic-pituitary-adrenal axis can be observed in patients with MS, showing altered cortisol levels. We aimed to identify basal cortisol levels and verify the relationship with clinical symptoms in patients with MS. A systematic search was conducted in the databases: Pubmed, Web of Science and SCOPUS. Both higher and lower cortisol levels were associated with MS. Higher cortisol levels were associated with depression and anxiety, while lower levels were associated with depression, fatigue and urinary dysfunction. Higher cortisol levels may be associated with the progression and severity of MS.

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