scholarly journals Role of Sex Hormones and Their Receptors on Gastric Nrf2 and Neuronal Nitric Oxide Function in an Experimental Hyperglycemia Model

2020 ◽  
Author(s):  
Jeremy Sprouse ◽  
Chethan Sampath ◽  
PANDU GANGULA
Keyword(s):  
Nitric Oxide ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Nuclear Factor ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Nnos Expression ◽  
In Vitro Treatment

Abstract Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

scholarly journals Role of Sex Hormones and Their Receptors on Gastric Nrf2 and Neuronal Nitric Oxide Synthase Function in an Experimental Hyperglycemia Model

2020 ◽  
Author(s):  
Jeremy Sprouse ◽  
Chethan Sampath ◽  
PANDU GANGULA
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Neuronal Nitric Oxide Synthase ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Nnos Expression

Abstract Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

scholarly journals Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jeremy Sprouse ◽  
Chethan Sampath ◽  
Pandu R. Gangula
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Neuronal Nitric Oxide Synthase ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Nnos Expression

Abstract Background Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods Gastric neuromuscular sections from adult female C57BL/6 J mice were incubated in normoglycemic (NG, 5 mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 h. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p < 0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

scholarly journals Role of Sex Hormones And Their Receptors On Gastric Nrf2 And Neuronal Nitric Oxide Synthase Function In An Experimental Hyperglycemia Model

2020 ◽  
Author(s):  
Jeremy Sprouse ◽  
Chethan Sampath ◽  
PANDU GANGULA
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Neuronal Nitric Oxide Synthase ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Nnos Expression

Abstract Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

scholarly journals Role of Sex Hormones And Their Receptors On Gastric Nrf2 And Neuronal Nitric Oxide Synthase Function In An Experimental Hyperglycemia Model

2019 ◽  
Author(s):  
Jeremy Sprouse ◽  
Chethan Sampath ◽  
PANDU GANGULA
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Neuronal Nitric Oxide Synthase ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Nnos Expression

Abstract Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia. Keywords: Gastroparesis; Sex Hormones; Estrogen Receptors; Drug Therapy; nNOS, Nrf2, Nitrergic Relaxation

scholarly journals Regulatory Role of GSK-3βon NF-κB, Nitric Oxide, and TNF-αin Group A Streptococcal Infection

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Yu-Tzu Chang ◽  
Chia-Ling Chen ◽  
Chiou-Feng Lin ◽  
Shiou-Ling Lu ◽  
Miao-Huei Cheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mouse Model ◽  
Group A Streptococcus ◽  
Glycogen Synthase ◽  
Critical Issue ◽  
No Production ◽  
Group A ◽  
Oxide Synthase

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β(GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3βin GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3βoccurred after GAS infection, and inhibition of GSK-3βreduced iNOS expression and NO production. Furthermore, GSK-3βinhibitors reduced NF-κB activation and subsequent TNF-αproduction, which indicates that GSK-3βacts upstream of NF-κB in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3βinhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-αand improved the survival rate. The inhibition of GSK-3βto moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

scholarly journals 108 THE ROLE OF NITRIC OXIDE SYNTHASE IN IN VITRO DEVELOPMENT OF BOVINE OOCYTES AND PRE-IMPLANTATION EMBRYOS

2005 ◽  
Vol 17 (2) ◽  
pp. 204
Author(s):  
A.K. Kadanga ◽  
D. Tesfaye ◽  
S. Ponsuksili ◽  
K. Wimmers ◽  
M. Gilles ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Culture Medium ◽  
Bovine Embryos ◽  
Nos Inhibitor ◽  
Blastocyst Rate ◽  
Oxide Synthase ◽  
Vitro Development ◽  
Bovine Oocytes

Nitric oxide (NO) is a free radical that serves as a key-signal molecule in various physiological processes including reproduction. Four isoforms of nitric oxide synthase (NOS) have been characterized: endothelial (eNOS), inducible (iNOS), neuronal (nNOS), and mitochondrial (mtNOS). The first two isoforms are reported to be expressed in mouse follicles, oocytes, and pre-implantation embryos (Nishikimi A et al. 2001 Reproduction 122, 957–963). However, the role of any of these isoforms have not yet been investigated in bovine embryos. Here we aimed to examine the role of NOS in in vitro development of bovine embryos by treating embryos with NOS inhibitor, N-omega-L-nitro-arginine methyl esther (L-NAME), and examining the localization of the protein in pre-implantation embryos. Oocytes and embryos were grown in the media with NOS inhibitor added at a level of 0 mM (control), 1 mM, and 10 mM to either maturation or culture medium. Each experiment was conducted in four replicates each containing 100 oocytes for IVP. Cleavage and blastocyst rate were recorded at Days 2 and 7, respectively. Data were analyzed using the General Linear Model in SAS version 8.02 (SAS Institute, Inc., Cary, NC, USA) with the main factors being the level of L-NAME and the point of application. Pairwise comparisons were done using the Tukey test. Protein localization in bovine oocytes and embryos was performed by immunocytochemistry using eNOS- and iNOS-specific antibodies. Embryos were fixed in 3.7% paraformaldehyde, permeabilized in 0.1% Triton-X100, and washed three times in PBS supplemented with BSA. They were incubated with eNOS and iNOS primary antibody (1:200 dilutions) and washed before incubation with secondary antibody conjugated to FITC. After washing they were mounted on glass slides and examined under a confocal laser scanning microscope (Carl Zeiss Jena, Carl Zeiss AG, Oberkochen, Germany). In the controls the primary antibodies were omitted. As shown in the table below, the presence of L-NAME in the maturation medium significantly reduced the cleavage and blastocyst rate independent of the dosage applied. However the presence of L-NAME in the culture medium had an influence only on the blastocyst rate. The immunocytochemical staining results showed that both eNOS and iNOS are expressed in the cytoplasm of the MII oocytes, and during the pre-implantation stage the fluorescence signal was observed in nuclei and cytoplasm. However, the nuclear signal was much weaker. In conclusion, the present study is the first to determine the role of NO and to detect NOS protein in bovine oocytes and pre-implantation embryos. These results indicate that nitric oxide may play an important role as diffusible regulator of bovine oocyte maturation and preimplantation embryo development. Table 1. Effect of l-name addition in maturation or culture medium on embryo development

scholarly journals Nitric oxide synthase acutely regulates progesterone production by in vitro cultured rabbit corpora lutea

1999 ◽  
Vol 160 (2) ◽  
pp. 275-283 ◽  
Author(s):  
A Gobbetti ◽  
C Boiti ◽  
C Canali ◽  
M Zerani
Keyword(s):  
Nitric Oxide ◽  
In Vitro Release ◽  
Inhibitory Effect ◽  
Corpora Lutea ◽  
No Donor ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Vitro Release

We examined the presence and the regulation of nitric oxide (NO) synthase (NOS) using in vitro cultured corpora lutea (CL) obtained from rabbits at days 4 and 9 of pseudopregnancy. The role of NO and NOS on steroidogenesis was also investigated using the same CL preparations after short-term incubations (30 min and 2 h) with the NO donor, sodium nitroprusside (NP), the NOS inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME) and prostaglandin (PG) F-2alpha. The basal NOS activity was greater in CL at day 4 than at day 9, and was also differently modulated by PGF-2alpha, depending on the age of the CL. The addition of PGF-2alpha to day 4 CL had no effect, but PGF-2alpha on day 9 caused a threefold increase in NOS activity. NP caused a two- to fivefold decrease in release of progesterone from CL of both ages, and this inhibitory effect on steroidogenesis was reversed by l-NAME. All treatments failed to modify basal androgens and 17beta-oestradiol was not detectable in either control or treated CL. These results suggest that NO is effectively involved in the regulation process of steroidogenesis, independently of 17beta-oestradiol. PGF-2alpha had no effect on day 4, but induced luteolysis on day 9, by reducing progesterone (P</=0. 01) to about 18% of control. The luteolytic action of PGF-2alpha was completely reversed by co-incubation with l-NAME, thus supporting the hypothesis that luteolysis is mediated by NO. The addition of NP or l-NAME did not modify the in vitro release of PGF-2alpha. We hypothesised that PGF-2alpha upregulates NOS activity and, consequently, the production of NO, which acutely inhibits progesterone release from day 9 CL of pseudopregnant rabbits.

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