Isoflurane stress induces glucocorticoid production in mouse lymphoid organs

2021 ◽  
Author(s):  
Jordan E Hamden ◽  
Melody Salehzadeh ◽  
Katherine M. Gray ◽  
Brandon J Forys ◽  
Kiran K Soma
Keyword(s):  
Adrenal Glands ◽  
Vehicle Control ◽  
Postnatal Period ◽  
Lymphoid Organs ◽  
Systemic Steroid ◽  
Potential Mechanism ◽  
Response To Stress ◽  
Glucocorticoid Production ◽  
Acute Stressor ◽  
Insight Into

Glucocorticoids (GCs) are secreted by the adrenal glands and locally produced by lymphoid organs. Adrenal GC secretion at baseline and in response to stressors is greatly reduced during the stress hyporesponsive period (SHRP) in neonatal mice (postnatal day (PND) 2-12). It is unknown whether lymphoid GC production increases in response to stressors during the SHRP. Here, we administered an acute stressor (isoflurane anesthesia) to mice before, during, and after the SHRP and measured systemic and local GCs via mass spectrometry. We administered isoflurane, vehicle control (oxygen), or neither (baseline) at PND 1, 5, 9, or 13 and measured progesterone and 6 GCs in blood, bone marrow, thymus, and spleen. At PND1, blood and lymphoid GC levels were high and did not respond to stress. At PND5, blood GC levels were very low and increased slightly after stress, while lymphoid GC levels were also low but, increased greatly after stress. At PND9, blood and lymphoid GC levels were similar at baseline and increased similarly after stress. At PND13, blood GC levels were higher than lymphoid GC levels at baseline, and blood GC levels showed a greater response to stress. These data demonstrate the remarkable plasticity of GC physiology during the postnatal period, show that local steroid levels do not reflect systemic steroid levels, provide insight into the SHRP, and identify a potential mechanism by which early-life stressors can alter immunity in adulthood.

Glucocorticoid production in lymphoid organs: Acute effects of lipopolysaccharide in neonatal and adult mice

Endocrinology ◽  
2021 ◽  
Author(s):  
Melody Salehzadeh ◽  
Jordan E Hamden ◽  
Michael X Li ◽  
Hitasha Bajaj ◽  
Ruolan S Wu ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Adrenal Glands ◽  
Lymphoid Organs ◽  
Acute Effects ◽  
Steroidogenic Enzymes ◽  
Steroidogenic Enzyme ◽  
Adult Mice ◽  
Liquid Chromatography Tandem Mass ◽  
Glucocorticoid Production ◽  
Local Expression

Abstract Glucocorticoids (GCs) are critical modulators of the immune system. The hypothalamic-pituitary-adrenal (HPA) axis regulates circulating GC levels and is stimulated by endotoxins. Lymphoid organs also produce GCs; however, it is not known how lymphoid GC levels are regulated in response to endotoxins. We assessed whether an acute challenge of lipopolysaccharide (LPS) increases lymphoid levels of GCs, steroidogenic enzymes expression, and components of the HPA axis (e.g., CRH) expression. We administered LPS (50µg/kg i.p.) or vehicle control to male and female C57BL/6J neonatal (post-natal day (PND) 5) and adult (PND90) mice and collected blood, bone marrow, thymus, and spleen 4 hr later. We measured progesterone, 11-deoxycorticosterone (DOC), corticosterone, and 11-dehydrocorticosterone (DHC) via liquid chromatography tandem mass spectrometry (LC-MS/MS). We measured gene expression of key steroidogenic enzymes (Cyp11b1, Hsd11b1, and Hsd11b2) and HPA axis components (Crh, Crhr1, Pomc, and Mc2r) via qPCR. At PND5, LPS induced greater increases in steroid levels in lymphoid organs than in blood. In contrast, at PND90, LPS induced greater increases in steroid levels in blood than in lymphoid organs. Steroidogenic enzyme transcripts were present in all lymphoid organs, and LPS altered steroidogenic enzyme expression predominately in the spleen. Lastly, we detected transcripts of key HPA axis components in all lymphoid organs, and there was an effect of LPS in the spleen. Taken together, these data suggest that LPS regulates GC production by lymphoid organs, similar to its effects on the adrenal glands, and the effects of LPS might be mediated by local expression of CRH and ACTH.

scholarly journals OR19-04 Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Melody Salehzadeh ◽  
Jordan Edward Hamden ◽  
Michael X Li ◽  
Hitasha Bajaj ◽  
Cathy Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hpa Axis ◽  
Anterior Pituitary ◽  
Adrenal Glands ◽  
Brain Regions ◽  
Lymphoid Organs ◽  
Thymocyte Development ◽  
Immune Systems ◽  
Immune System Development ◽  
Glucocorticoid Production

Abstract Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog The hypothalamic-pituitary-adrenal (HPA) axis is a critical stress response system in vertebrates. The hypothalamus secretes corticotropin-releasing hormone (CRH), which binds its receptor (CRH-R1) in the anterior pituitary. The anterior pituitary then secretes adrenocorticotropic hormone (ACTH), which binds its receptor (MC2R) in the adrenal glands and stimulates secretion of glucocorticoids into the bloodstream. Glucocorticoids are critical modulators of neural and immune system development. During early development (postnatal day (PND) 2 to 12), mice show decreased adrenal glucocorticoid secretion at baseline and in response to stressors, termed the stress hyporesponsive period (SHRP) (1). Traditionally, glucocorticoids have been thought to be synthesized only in the adrenal glands. However, recent evidence demonstrates that glucocorticoids are also produced in extra-adrenal tissues, such as the brain and lymphoid organs (2). This may be of particular importance during the SHRP, as local production allows glucocorticoid modulation of specific tissues and cells, without general effects throughout the organism. Importantly, the factors that regulate local glucocorticoid production remain unknown. To study the regulation of local glucocorticoid production, we examined whether mediators of the HPA axis are locally expressed at baseline and in response to an immune stressor. We assessed systemic and local glucocorticoid levels in neonatal (PND5) C57BL/6J mice 4hr after an immune challenge with lipopolysaccharide (50µg/kg i.p.) or vehicle control. We examined blood, microdissected brain regions (prefrontal cortex, hippocampus, hypothalamus), and lymphoid organs (thymus, spleen, bone marrow). A panel of 7 steroids was measured via liquid chromatography tandem mass spectrometry (LC-MS/MS). Gene expression of Crh, Crh-R1, Pomc, and Mc2r was quantified via qPCR. Preliminary data indicate that corticosterone was 2-fold higher in tissues than in blood after an immune stressor. The thymus expressed all genes of interest, supporting the existence of a local HPA axis “homolog” in the thymus. Brain, spleen and bone marrow expressed a subset of the genes of interest. These exciting data demonstrate that all the mediators of the HPA axis are locally expressed within the thymus, likely to regulate thymocyte development and reactivity. Greater understanding of local glucocorticoid production will provide crucial insight into neural and immune development and function. Reference: (1) Sapolsky et al., Brain Res Rev. 1986 11(1):65–76. (2) Taves et al., Endocrinology. 2015 156(2):511–522.

Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension

Physiology ◽  
2007 ◽  
Vol 22 (4) ◽  
pp. 252-260 ◽  
Author(s):  
Amy M. Jonk ◽  
Alfons J. H. M. Houben ◽  
Renate T. de Jongh ◽  
Erik H. Serné ◽  
Nicoloaas C. Schaper ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Microvascular Dysfunction ◽  
Important Risk Factor ◽  
Potential Mechanism ◽  
The Metabolic Syndrome ◽  
New Treatments ◽  
Insight Into

Obesity is an important risk factor for insulin resistance and hypertension and plays a central role in the metabolic syndrome. Insight into the pathophysiology of this syndrome may lead to new treatments. This paper has reviewed the evidence for an important role for the microcirculation as a possible link between obesity, insulin resistance and hypertension.

scholarly journals Anticoagulants and the Hemostatic System: A Primer for Occupational Stress Researchers

2021 ◽  
Vol 18 (20) ◽  
pp. 10626
Author(s):  
Eamonn Arble ◽  
Bengt B. Arnetz
Keyword(s):  
Occupational Stress ◽  
Blood Clotting ◽  
Biological Process ◽  
Occupational Functioning ◽  
System A ◽  
Hemostatic System ◽  
Response To Stress ◽  
Occupational Strain ◽  
Potential Methods ◽  
Insight Into

Anticoagulation, the body’s mechanism to prevent blood clotting, is an internal biomarker of an individual’s response to stress. Research has indicated that understanding the causes, processes, and consequences of anticoagulation can provide important insight into the experience of individuals facing emotional and occupational strain. Unfortunately, despite their importance, the mechanisms and implications of anticoagulation are unfamiliar to many researchers and practitioners working with trauma-exposed professionals. This paper provides an accessible primer on the topic of anticoagulation, including an overview of the biological process, the research connecting these processes with emotional and occupational functioning, as well as some potential methods for assessment.

scholarly journals CaMKII Potentiates Store-Operated Ca2+ Entry Through Enhancing STIM1 Aggregation and Interaction with Orai1

2018 ◽  
Vol 46 (3) ◽  
pp. 1042-1054 ◽  
Author(s):  
Shu Li ◽  
Jingyi Xue ◽  
Zhipeng Sun ◽  
Tiantian Liu ◽  
Lane Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Confocal Microscopy ◽  
Specific Inhibitor ◽  
Potential Mechanism ◽  
Additional Insight ◽  
Dependent Protein Kinase ◽  
Store Depletion ◽  
Selective Channel ◽  
Dependent Protein ◽  
Insight Into

Background/Aims: Upon Ca2+ store depletion, stromal interaction molecule 1 (STIM1) oligomerizes, redistributes near plasmalemma to interact with Ca2+ selective channel-forming subunit (Orai1) and initiates store-operated Ca2+ entry (SOCE). Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a regulator of SOCE, but how CaMKII regulates SOCE remains obscure. Methods: Using Fura2, confocal microscopy, co-immunoprecipitation, specific blocker and overexpression/knockdown approaches, we evaluated STIM1 aggregation and its interaction with Orai1, and SOCE upon Ca2+ store depletion in thapsigargin (TG) treated HEK293 and HeLa cells. Results: Overexpression of CaMKIIδ enhanced TG-induced STIM1 co-localization and interaction with Orai1 as well as SOCE. In contrast, CaMKIIδ knockdown and a specific inhibitor of CaMKII suppressed them. In addition, overexpression or knockdown of CaMKIIδ in TG treated cells exhibited increased or reduced STIM1 clustering and plasmalemma redistribution, respectively. Conclusion: CaMKII up-regulates SOCE by increasing STIM1 aggregation and interaction with Orai1. This study provides an additional insight into SOCE regulation and a potential mechanism for CaMKII involvement in some pathological situations through crosstalk with SOCE.

scholarly journals Coordination of cohabiting phage elements supports bacteria–phage cooperation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tal Argov ◽  
Shai Ran Sapir ◽  
Anna Pasechnek ◽  
Gil Azulay ◽  
Olga Stadnyuk ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Bacterial Pathogens ◽  
Molecular Switch ◽  
Complex Environments ◽  
Phage Tail ◽  
Bacterial Lysis ◽  
Viral Particles ◽  
Response To Stress ◽  
Insight Into

AbstractBacterial pathogens often carry multiple prophages and other phage-derived elements within their genome, some of which can produce viral particles in response to stress. Listeria monocytogenes 10403S harbors two phage elements in its chromosome, both of which can trigger bacterial lysis under stress: an active prophage (ϕ10403S) that promotes the virulence of its host and can produce infective virions, and a locus encoding phage tail-like bacteriocins. Here, we show that the two phage elements are co-regulated, with the bacteriocin locus controlling the induction of the prophage and thus its activity as a virulence-associated molecular switch. More specifically, a metalloprotease encoded in the bacteriocin locus is upregulated in response to stress and acts as an anti-repressor for CI-like repressors encoded in each phage element. Our results provide molecular insight into the phenomenon of polylysogeny and its intricate adaptation to complex environments.

scholarly journals Development of Adrenocorticotrophic Hormone Cells of Adenohypophysis–Adrenal Cortex Axis of Long-tailed Monkey (Macaca fascicularis) during Pre and Postnatal Period

2008 ◽  
Vol 2 (2) ◽  
Author(s):  
Nurhidayat Nurhidayat ◽  
Ika K. Syarifah ◽  
Supratikno Supratikno ◽  
Sri Wahyuni
Keyword(s):  
Adrenal Cortex ◽  
Macaca Fascicularis ◽  
Adrenal Glands ◽  
Postnatal Period ◽  
Whole Body ◽  
Central Vein ◽  
Proliferation And Differentiation ◽  
Relationship Of ◽  
The Relationship ◽  
Hematoxylin Eosin

The objective of this study is to observe the relationship of development of adrenocorticotropic hormone (ACTH) cells of adenohypophysis–adrenal cortex axis during pre and postnatal period of longtailed monkey (Macaca fascicularis). Five fetuses aged 70, 85, 100, 120, and 150 days of gestation and 2new born aged 10 and 105 days old were used as research materials. The sections of the pituitary gland stained immunohistochemically using human ACTH antiserum and the adrenal glands stained by Hematoxylin-Eosin procedures. At the fetus 120 days old, the ACTH cells and blood vessel of fetaladenohypophysis developed well and its similar that found in older age. This condition suggested distributing the ACTH to whole body optimally. At the same time, the adrenal cortex cells of fetus 120 days old were active in proliferation and differentiation processes to form transition zone that lies between definitive and fetal zones, and central vein also developed in adrenal gland. In fetus aged 150 days, the cortex adrenal structure was similar with found in older fetus. The adenohypophysis ACTH cells developed earlier than adrenal cortex and their secretion suggested influencing the development of adrenal cortex cells of long-tailed monkey.

scholarly journals Insight into the Effects of Sous Vide on Cathepsin B and L Activities, Protein Degradation and the Ultrastructure of Beef

Foods ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1441
Author(s):  
Yantao Yin ◽  
Jailson Pereira ◽  
Lei Zhou ◽  
Jose M. Lorenzo ◽  
Xiaona Tian ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Sarcomere Length ◽  
Cathepsin L ◽  
Myofibrillar Protein ◽  
Potential Mechanism ◽  
Beef Tenderness ◽  
Fragmentation Index ◽  
Sous Vide ◽  
Hydrolysis Of ◽  
Insight Into

This study aimed to evaluate the effects of sous vide cooking (SV) on beef tenderness and its underlying potential mechanism. Beef semimembranosus (SM) were subjected to SV treatments at 45 °C, 55 °C and 65 °C for 4 h. Compared with control samples (CK, cooked at 75 °C until a core temperature of 72 °C was attained), SV treatment significantly promoted the release of cathepsin B and cathepsin L from lysosomes and decreased the shear force of beef SM (p < 0.05). In comparison with CK, samples treated with SV had more hydrolysis of myosin heavy chain and obtained higher myofibrillar fragmentation index, collagen solubility as well as longer sarcomere length (p < 0.05). The current study showed that the proteolysis of myofibrillar protein and collagen induced by cathepsin B and cathepsin L, and the limited longitudinal shrinkage together contributed to the improvement of beef tenderness upon SV.

scholarly journals Effect of the AM Fungus Sieverdingia tortuosa on Common Vetch Responses to an Anthracnose Pathogen

2020 ◽  
Vol 11 ◽  
Author(s):  
Tingting Ding ◽  
Weizhen Zhang ◽  
Yingde Li ◽  
Tingyu Duan
Keyword(s):  
Arbuscular Mycorrhizal ◽  
Chitinase Activity ◽  
Mapk Signaling ◽  
Common Vetch ◽  
Kegg Pathways ◽  
Phenylpropanoid Biosynthesis ◽  
Response To Stress ◽  
Am Fungus ◽  
Plant Pathogen Interactions ◽  
Insight Into

Colletotrichum lentis Damm causes anthracnose in Vicia sativa L, otherwise known as common vetch. It was first reported in China in 2019. This study evaluates the effects of the arbuscular mycorrhizal (AM) fungus Sieverdingia tortuosa (N.C. Schenck &amp; G.S. Sm.) Błaszk., Niezgoda, &amp; B.T. Goto on growth and disease severity in common vetch. Our main finding is that the AM fungus increased root biomass and reduced anthracnose severity of common vetch. Responses correlated with defense, such as chitinase activity, polyphenol oxidase (PPO) activity, the concentrations of jasmonic acid and proline, and the expression of resistance-related genes (e.g., upregulated “signal transduction,” “MAPK signaling pathway,” “chitinase activity,” “response to stress,” and the KEGG pathways “phenylpropanoid biosynthesis,” “MAPK signaling pathways,” and “plant-pathogen interactions”), were also affected These findings provide insight into the mechanism by which this AM fungus regulates the defense response of common vetch to C. lentis.

Abstract 147: Hepatic Scavenger Receptor BI Protects Against Polymicrobial-Induced Sepsis Through Promoting LPS Clearance in Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Ling Guo ◽  
Zhong Zheng ◽  
Junting Ai ◽  
Bin Huang ◽  
Xiang-An Li
Keyword(s):  
Protective Factor ◽  
Adrenal Glands ◽  
Cytokine Production ◽  
Scavenger Receptor ◽  
Cecal Ligation ◽  
Protective Role ◽  
Bacterial Clearance ◽  
Inflammatory Cytokine Production ◽  
Scavenger Receptor Bi ◽  
Glucocorticoid Production

Recent studies revealed that scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. However, the mechanisms underlying this protection remain largely unknown. In this study, using Scarb1 I179N mice, a mouse model specifically deficient in hepatic SR-BI, we report that hepatic SR-BI protects against cecal ligation and puncture (CLP)-induced sepsis as shown by 75% fatality in Scarb1 I179N mice, but only 21% fatality in C57BL/6J control mice. The increase in fatality in Scarb1 I179N mice was associated with an exacerbated inflammatory cytokine production. Further study demonstrated that hepatic SR-BI exerts its protection against sepsis through its role in promoting LPS clearance without affecting the inflammatory response in macrophages, the glucocorticoid production in adrenal glands, the leukocyte recruitment to peritoneum or the bacterial clearance in liver. Our findings reveal hepatic SR-BI as a critical protective factor in sepsis and point out that promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis.

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