Nitric oxide : biology and chemistry最新文献

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The relationship of nitric oxide synthase 3(NOS3) gene polymorphism in the risk of pulmonary arterial hypertension: A systematic review and meta-analysis 一氧化氮合成酶 3(NOS3) 基因多态性与肺动脉高压风险的关系:系统回顾与元分析》。
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-22 DOI: 10.1016/j.niox.2024.11.009
Kang Yi , Tao Guo , Wen-Xin Wang , Shao-E He , Xin Zhang , Jian-Guo Xu , Zi-Qiang Wang , Fan-Ning Wang , Tao You
{"title":"The relationship of nitric oxide synthase 3(NOS3) gene polymorphism in the risk of pulmonary arterial hypertension: A systematic review and meta-analysis","authors":"Kang Yi , Tao Guo , Wen-Xin Wang , Shao-E He , Xin Zhang , Jian-Guo Xu , Zi-Qiang Wang , Fan-Ning Wang , Tao You","doi":"10.1016/j.niox.2024.11.009","DOIUrl":"10.1016/j.niox.2024.11.009","url":null,"abstract":"<div><h3>Background</h3><div>We performed the present study to better elucidate the correlation of nitric oxide synthase 3 (NOS3) gene polymorphism with the risk of pulmonary arterial hypertension (PAH).</div></div><div><h3>Material/methods</h3><div>According to the designed search strategy, a systematic literature search was performed through the PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP and Wan Fang databases to collect published case-control studies on the correlation between NOS3 gene polymorphism and PAH. The search deadline was December 26, 2023. Two reviewers independently screened the literature, extracted data and evaluated the quality according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. The odds ratio (OR) and 95 % confidence interval (CI) of the genotype distribution were used as the effect indicators.</div></div><div><h3>Results</h3><div>A total of 11 eligible studies were included, involving three single nucleotide polymorphism (SNP) sites of the NOS3 gene: G894T (rs1799983), 4b/4a (rs61722009), and T-786C (rs2070744). The meta-analysis revealed that for PAH analysis, 4 genetic models of NOS3 G894T polymorphism increased the risk of PAH: the allele model (T vs G, OR = 1.9, 95%CI [1.16, 3.11],P = 0.01), the homozygote model (GG vs TT, OR = 1.91, 95%CI [1.04, 3.51], P = 0.04), the heterozygote model (GG vs GT, OR = 3.19, 95%CI [1.65, 6.19], P = 0.0006) and the dominant model (GT + TT vs GG, OR = 3.06, 95%CI [1.54, 6.09], P = 0.001). In the subgroups analysis, the NOS3 G894T polymorphism was found to be associated with the risk of PAH subgroups, including CHD combined with PAH and COPD combined with PAH, Particularly, there is a highly significant correlation with CHD combined with PAH. 2 genetic models of NOS3 4b/4a polymorphism increased the risk of PAH: the homozygote model (BB vs AA, OR = 2.1, 95%CI [1.02, 4.35], P = 0.04) and the recessive model (BB + BA vs AA, OR = 2.55, 95%CI [1.27, 5.11], P = 0.009). In the subgroups analysis, the NOS3 4b/4a polymorphism was found to be associated with the susceptibility of CHD combined with PAH. The results of the combined analysis of each gene model of NOS3 T-786C gene polymorphism sites were not statistically significant, and their P values were all>0.05. The NOS3 G894T and NOS3 4b/4a gene polymorphism had been found to be associated with the risk of PAH in different regional and racial subgroups. In contrast to the NOS3 G894T gene polymorphism, which increased the risk of PAH development in the yellow race subgroup, the NOS3 4b/4a gene polymorphism reduced the risk of PAH development in the white race subgroup and was a protective factor.</div></div><div><h3>Conclusions</h3><div>The NOS3 G894T (rs1799983) and NOS3 4b/4a (rs61722009) gene polymorphism have a strong correlation with the risk of PAH, with this association varying among different regions and ethnicities. However, it is still necessary to expand the sample ","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 51-76"},"PeriodicalIF":3.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Critical role of hydrogen sulfide in the management of neurodegenerative disease. 硫化氢在治疗神经退行性疾病中的关键作用。
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-20 DOI: 10.1016/j.niox.2024.11.006
Rajashree Pawar, Dheeraj Pandey, Saba Naqvi, Abha Sharma
{"title":"Critical role of hydrogen sulfide in the management of neurodegenerative disease.","authors":"Rajashree Pawar, Dheeraj Pandey, Saba Naqvi, Abha Sharma","doi":"10.1016/j.niox.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.niox.2024.11.006","url":null,"abstract":"<p><p>Hydrogen sulfide has been known to humans for about 300 years and the previous studies emphasize only its toxic side effects. In the last two decennium, researchers have varied their perspectives and insights towards H<sub>2</sub>S biology based on experimental findings. It has been found that H<sub>2</sub>S is an endogenic gaseous signaling molecule in many organisms and plays a crucial role in many systems and diseases. Early reports suggest that H<sub>2</sub>S as a neuromodulator influences calcium levels within the brain cells which ultimately control memory, learning, and cognition. It has also been observed that some complications in the pathogenesis of neurodegenerative diseases are due to anomalies in the biosynthesis and metabolism of H<sub>2</sub>S. This review focuses on the role of H<sub>2</sub>S in the pathophysiology of major neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Vascular dementia. H<sub>2</sub>S was observed to have a protective role in the above-mentioned neurological conditions and the H<sub>2</sub>S donor therapy may help in disease management. The H<sub>2</sub>S gas displays a neuroprotective role and protects against cellular damage thereby declining the neurological conditions. Some studies have revealed that treatment with H<sub>2</sub>S donors has improved neuronal damage, restored memory and cognition in animal models. In this review, we have discussed the role of H<sub>2</sub>S donors as neuroprotective agents with examples of some of the natural and synthetic H<sub>2</sub>S donors, and also briefly enumerated the molecules used to detect H<sub>2</sub>S in neurodegenerative diseases.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nitric oxide and mitochondrial function in cardiovascular diseases 心血管疾病中的一氧化氮和线粒体功能
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-20 DOI: 10.1016/j.niox.2024.11.007
Haoqi Li , Zijie Cheng , Dan Wu , Qingxun Hu
{"title":"Nitric oxide and mitochondrial function in cardiovascular diseases","authors":"Haoqi Li ,&nbsp;Zijie Cheng ,&nbsp;Dan Wu ,&nbsp;Qingxun Hu","doi":"10.1016/j.niox.2024.11.007","DOIUrl":"10.1016/j.niox.2024.11.007","url":null,"abstract":"<div><div>Nitric oxide (NO) has been highlighted as an important factor in cardiovascular system. As a signaling molecule in the cardiovascular system, NO can relax blood vessels, lower blood pressure, and prevent platelet aggregation. Mitochondria serve as a central hub for cellular metabolism and intracellular signaling, and their dysfunction can lead to a variety of diseases. Accumulating evidence suggests that NO can act as a regulator of mitochondria, affecting mitochondrial function and cellular activity, which in turn mediates the onset and progression of disease. However, there is a lack of comprehensive understanding of how NO regulates mitochondrial function in the cardiovascular system. This review aims to summarize the regulation of mitochondrial function by nitric oxide in cardiovascular related diseases, as well as the multifaceted and complex roles of NO in the cardiovascular system. Understanding the mechanism of NO mediated mitochondrial function can provide new insights for the prevention and treatment of cardiovascular diseases.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 42-50"},"PeriodicalIF":3.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing S-nitrosoglutathione reductase decreases S-nitrosylation of ERO1α and reduces neuronal death in secondary traumatic brain injury 增强 S-亚硝基谷胱甘肽还原酶可降低ERO1α的 S-亚硝基化并减少继发性创伤性脑损伤的神经元死亡
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-19 DOI: 10.1016/j.niox.2024.11.005
Guangjie Liu , Dengfeng Lu , Jie Wu , Shixin Wang , Aojie Duan , Yubo Ren , Yu Zhang , Lei Meng , Renjie Shou , Haiying Li , Zhong Wang , Zongqi Wang , Xiaoou Sun
{"title":"Enhancing S-nitrosoglutathione reductase decreases S-nitrosylation of ERO1α and reduces neuronal death in secondary traumatic brain injury","authors":"Guangjie Liu ,&nbsp;Dengfeng Lu ,&nbsp;Jie Wu ,&nbsp;Shixin Wang ,&nbsp;Aojie Duan ,&nbsp;Yubo Ren ,&nbsp;Yu Zhang ,&nbsp;Lei Meng ,&nbsp;Renjie Shou ,&nbsp;Haiying Li ,&nbsp;Zhong Wang ,&nbsp;Zongqi Wang ,&nbsp;Xiaoou Sun","doi":"10.1016/j.niox.2024.11.005","DOIUrl":"10.1016/j.niox.2024.11.005","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) has the highest incidence of all common neurological disorders, along with high mortality and disability rates. Pathological conversion of excess nitric oxide (NO) to S-nitrosoglutathion (GSNO) after TBI leads to high S-nitrosylation of intracellular proteins, causing nitrative stress. GSNO reductase (GSNOR) plays an important role by regulating GSNO and SNO-proteins (PSNOs) and as a redox regulator of the nervous system. However, the effect of GSNOR on protein S-nitrosylation in secondary brain injury after TBI is not clear. <em>In vivo</em> TBI model was established in male C57BL/6 mice via controlled cortical impact (CCI). Neuron-targeted GSNOR-overexpression adeno-associated virus (AAV) was constructed and administered to mice by stereotactic cortical injection. The results showed that NO, GSNO, neuronal protein S-nitrosylation and neuronal death increased after TBI, while the level and activity of GSNOR decreased. Overexpression of GSNOR by AAV decreased GSNO and NO and improved short-term neurobehavioral outcomes in mice. GSNOR overexpression can reduce endoplasmic reticulum stress and neuronal death by reducing the S-nitrosylation of ERO1α via H<sub>2</sub>O<sub>2</sub> generation and plays a neuroprotective role. In conclusion, our results suggest that GSNOR regulating S-nitrosylation of ERO1α may participate in neuronal death, and overexpression of GSNOR in neurons after experimental brain injury alleviates secondary brain injury. Our research provides a potential therapeutic approach for the treatment of TBI.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 29-41"},"PeriodicalIF":3.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigation of the susceptibility of clinical infection loads to nitric oxide antibacterial treatment 临床感染负荷对一氧化氮抗菌治疗敏感性的调查。
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-17 DOI: 10.1016/j.niox.2024.11.003
Lori M. Estes Bright , Arnab Mondal , Vicente Pinon , Anil Kumar , Stephen Thompson , Elizabeth J. Brisbois , Hitesh Handa
{"title":"Investigation of the susceptibility of clinical infection loads to nitric oxide antibacterial treatment","authors":"Lori M. Estes Bright ,&nbsp;Arnab Mondal ,&nbsp;Vicente Pinon ,&nbsp;Anil Kumar ,&nbsp;Stephen Thompson ,&nbsp;Elizabeth J. Brisbois ,&nbsp;Hitesh Handa","doi":"10.1016/j.niox.2024.11.003","DOIUrl":"10.1016/j.niox.2024.11.003","url":null,"abstract":"<div><div>The persistent infection of medical devices by opportunistic pathogens has led to the development of antimicrobial medical device polymers. Nitric oxide (NO) is an endogenous antimicrobial molecule that is released through the degradation of synthetic donor molecules such as <em>S</em>-nitroso-<em>N</em>-acetylpenicillamine (SNAP) embedded into polymer membranes. It is hypothesized that the clinical success of these polymers is enhanced by the physiological release of NO and the consequent prevention of infection. However, such NO-releasing materials have never been evaluated against microbial loads that are commensurate with clinical infection levels. This study aimed to develop a standardized polymer film impregnated with SNAP that consistently releases NO and evaluates its efficacy against bacterial loads that represent clinical infection parameters. Microbial loads of 10<sup>3</sup>, 10<sup>5</sup>, and 10<sup>8</sup> (colony-forming units) CFU mL<sup>−1</sup> were exposed to the NO-releasing polymer, corresponding to bloodstream infections, catheter-associated urinary tract infections, and standard laboratory exposure levels that have been reported in the scientific literature. By 24 h, SNAP films led to &gt;1 log reduction of adhered and viable <em>E. coli</em> at all tested microbial loads compared to control polydimethylsiloxane (PDMS). Further, SNAP films displayed no viable adhered <em>S. aureus</em> at the 10<sup>3</sup> microbial level for the entire study and showed total planktonic killing by 8 h. NO localization within bacterial cells adhering to the films was evaluated, revealing higher NO uptake and consequent bacterial killing by SNAP samples. This unique study shows that NO-releasing polymers not only kill bacteria adhered to the polymer surface, but localized delivery leads to environmental planktonic bacterial killing that prevents adhesion from occurring. Furthermore, the promising findings of NO-releasing polymers in scientific research indicate their potential for successful application in clinical settings to prevent infections.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 19-28"},"PeriodicalIF":3.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
KLF4's Role in Regulating Nitric Oxide Production and Promoting Microvascular Formation Following Ischemic Stroke. KLF4 在缺血性脑卒中后调节一氧化氮生成和促进微血管形成中的作用
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-16 DOI: 10.1016/j.niox.2024.11.004
Kuo Li, Chuansuo Zhang, Li Xuan Wang, Xiaoxuan Wang, Ruyue Wang
{"title":"KLF4's Role in Regulating Nitric Oxide Production and Promoting Microvascular Formation Following Ischemic Stroke.","authors":"Kuo Li, Chuansuo Zhang, Li Xuan Wang, Xiaoxuan Wang, Ruyue Wang","doi":"10.1016/j.niox.2024.11.004","DOIUrl":"10.1016/j.niox.2024.11.004","url":null,"abstract":"<p><p>This study examines KLF4's role in endothelial cells (ECs), emphasizing its effects on nitric oxide (NO) production, microvascular formation, and oxidative stress regulation following ischemic stroke. Through high-throughput sequencing, we identified eight cell subpopulations in carotid artery tissues post-stroke, with KLF4 notably elevated in ECs. KLF4 overexpression in ECs promoted NO synthesis, enhanced endothelial tube formation, mitigated oxidative stress, and improved smooth muscle cells (SMCs) function, collectively boosting blood flow in ischemic regions. These findings highlight KLF4 as pivotal in vascular regeneration and oxidative stress reduction, positioning it as a promising target for cardiovascular and cerebrovascular therapies.</p>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exogenous sodium nitroprusside exhibits multiple positive roles in alleviating cadmium toxicity in tobacco (Nicotiana tabacum L.) 外源性硝普钠在缓解烟草(Nicotiana tabacum L.)镉毒性中发挥多重积极作用
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-14 DOI: 10.1016/j.niox.2024.11.002
Kejin Song , Hongwei Li , Kunjian Yang , Tengfei Ma , Yingying Hu , Ji Chen , Shunqin Zhu , Wanhong Liu
{"title":"Exogenous sodium nitroprusside exhibits multiple positive roles in alleviating cadmium toxicity in tobacco (Nicotiana tabacum L.)","authors":"Kejin Song ,&nbsp;Hongwei Li ,&nbsp;Kunjian Yang ,&nbsp;Tengfei Ma ,&nbsp;Yingying Hu ,&nbsp;Ji Chen ,&nbsp;Shunqin Zhu ,&nbsp;Wanhong Liu","doi":"10.1016/j.niox.2024.11.002","DOIUrl":"10.1016/j.niox.2024.11.002","url":null,"abstract":"<div><div>As a donor of the gaseous signaling molecule nitric oxide (NO), sodium nitroprusside (SNP) has been shown to play a positive role in enhancing plant resistance to abiotic stress. However, its role in alleviating cadmium (Cd) toxicity in tobacco (<em>Nicotiana tabacum</em> L.) is not fully understood. This study found that Cd stress significantly inhibited tobacco growth. At the same time, 150 μM SNP was the most effective concentration in alleviating Cd toxicity in seedlings, restoring three stress tolerance indicators—MDA, H<sub>2</sub>O<sub>2</sub>, and proline—to control levels. Exogenous SNP mitigated Cd-induced oxidative stress by promoting the accumulation of non-enzymatic antioxidants (total phenolics and flavonoids) and activating key antioxidant enzymes (SOD, CAT, POD, APX, and GR) along with their gene expression. SNP also facilitated Cd accumulation in the root cell wall and prevented Cd translocation from roots to shoots. Additionally, SNP altered Cd's subcellular distribution, promoting its sequestration in vacuoles and cell walls, which may be related to the NO-mediated upregulation of the metallothionein gene <em>NtMT2F</em> and the phytochelatin gene <em>NtPCS2</em>. The addition of SNP significantly increased the proportion of Cd in less toxic chemical forms, with the residual Cd fraction in the Cd + SNP group reaching 7.30 %, higher than the 4.86 % in the Cd-only group. Furthermore, exogenous SNP counteracted Cd's inhibition of nitrate reductase (NR) activity, promoting endogenous NO production. This study systematically reveals the positive roles of exogenous SNP in mitigating Cd toxicity in tobacco, offering valuable insights for producing low-Cd tobacco.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 8-18"},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Downregulation of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus in Ins2Akita-type-1 diabetic mice contributes to sympatho-excitation Ins2Akita-1型糖尿病小鼠室旁核内神经元一氧化氮合酶(nNOS)的下调有助于交感神经兴奋。
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-11-07 DOI: 10.1016/j.niox.2024.11.001
Tapan A. Patel , Lie Gao , Shane H. Boomer , Xuefei Liu , Kaushik P. Patel , Hong Zheng
{"title":"Downregulation of neuronal nitric oxide synthase (nNOS) within the paraventricular nucleus in Ins2Akita-type-1 diabetic mice contributes to sympatho-excitation","authors":"Tapan A. Patel ,&nbsp;Lie Gao ,&nbsp;Shane H. Boomer ,&nbsp;Xuefei Liu ,&nbsp;Kaushik P. Patel ,&nbsp;Hong Zheng","doi":"10.1016/j.niox.2024.11.001","DOIUrl":"10.1016/j.niox.2024.11.001","url":null,"abstract":"<div><div>Activation of both renin-angiotensin system (RAS) and the sympathetic system is the primary etiologic event in developing cardiovascular complications in diabetes mellitus (DM). However, the precise mechanisms for sympathetic activation in DM have not been elucidated. Here we attempted to investigate diabetes-linked cardiovascular dysregulation due to angiotensin II (Ang II)-mediated reduction in neuronal nitric oxide (NO) synthase (nNOS) within the paraventricular neuleus (PVN). In the present study, we used Ins2<sup>+/−</sup>Akita (a spontaneous, insulin-dependent genetic diabetic non-obese murine model) and wild-type (WT) littermates mice as controls. At 14 weeks of age, we found the Akita mice had increased renal sympathetic nerve activity and elevated levels of plasma norepinephrine. There was decreased expression of nNOS protein (Akita 0.43 ± 0.11 vs. WT 0.75 ± 0.05, P &lt; 0.05) in the PVN of Akita mice. Akita mice had increased expression of angiotensin-converting enzyme (ACE) (Akita 0.58 ± 0.05 vs. WT 0.34 ± 0.04, P &lt; 0.05) and Ang II type 1 receptor (Akita 0.49 ± 0.03 vs. WT 0.29 ± 0.09, P &lt; 0.05), decreased expressions of ACE2 (Akita 0.17 ± 0.05 vs. WT 0.27 ± 0.03, P &lt; 0.05) and angiotensin (1–7) Mas receptor (Akita 0.46 ± 0.02 vs. WT 0.77 ± 0.07, P &lt; 0.05). Futher, there were increased protein levels of protein inhibitor of nNOS (PIN) (Akita 1.75 ± 0.08 vs. WT 0.71 ± 0.09, P &lt; 0.05) with concomitantly decreased catalytically active dimers of nNOS (Akita 0.11 ± 0.04 vs. WT 0.19 ± 0.02, P &lt; 0.05) in the PVN in Akita mice. Our studies suggest that activation of the excitatory arm of RAS, leads to a decrease NO, causing an over-activation of the sympathetic drive in DM.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"154 ","pages":"Pages 1-7"},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurogenic-derived 6-nitrodopamine is the most potent endogenous modulator of the mouse urinary bladder relaxation 神经源性 6-硝基多巴胺是小鼠膀胱松弛最有效的内源性调节剂
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-10-19 DOI: 10.1016/j.niox.2024.10.010
Mariana Gonçalves de Oliveira , José Britto-Junior , Douglas Rafael Martins Dias , Luise Gabriela Santos Pereira , Silvana Chiavegatto , Idam Hermawan , Hiroaki Shimokawa , Masato Tsutsui , Edson Antunes , Gilberto De Nucci
{"title":"Neurogenic-derived 6-nitrodopamine is the most potent endogenous modulator of the mouse urinary bladder relaxation","authors":"Mariana Gonçalves de Oliveira ,&nbsp;José Britto-Junior ,&nbsp;Douglas Rafael Martins Dias ,&nbsp;Luise Gabriela Santos Pereira ,&nbsp;Silvana Chiavegatto ,&nbsp;Idam Hermawan ,&nbsp;Hiroaki Shimokawa ,&nbsp;Masato Tsutsui ,&nbsp;Edson Antunes ,&nbsp;Gilberto De Nucci","doi":"10.1016/j.niox.2024.10.010","DOIUrl":"10.1016/j.niox.2024.10.010","url":null,"abstract":"<div><div>6-Nitrodopamine (6-ND) modulates vas deferens, seminal vesicles, and corpus cavernosum contractility; however, its role on the lower urinary tract organs has not been evaluated. Investigations of isolated urinary bladders from wild-type (WT) mice revealed 6-ND release was comparable to that of dopamine and adrenaline, whereas noradrenaline was hardly detected, as assessed by liquid chromatography coupled to tandem mass spectrometry. <em>In vitro</em>, 6-ND induced concentration-dependent relaxations in carbachol pre-contracted bladders with high potency (pEC<sub>50</sub>: 8.04 ± 0.86), independently of eNOS/sGC activity. Co-incubation of 6-ND (1–10 μM) antagonizes the contractile effects of acetylcholine (p &lt; 0.05). Experiments using nitric oxide synthase (NOS) knockout mice demonstrated that 6-ND release from isolated urinary bladder was significantly reduced by neuronal NOS (nNOS<sup>−/−</sup>) deletion and abolished by triple NOSs deletion (n/i/eNOS<sup>−/−</sup>), while no significant changes were observed in endothelial (eNOS<sup>−/−</sup>) or inducible (iNOS<sup>−/−</sup>) knockout mice. Incubation with tetrodotoxin resulted in a significant decrease in 6-ND release in bladders obtained from WT, but not in nNOS<sup>−/−</sup> mice. The bladders from nNOS<sup>−/−</sup> and n/i/eNOS<sup>−/−</sup> mice exhibited significantly higher contractile responses to electric field stimulation (EFS), compared to eNOS<sup>−/−</sup>, iNOS<sup>−/−</sup>, or WT bladders. The hyperreactivity observed in triple NOS knockouts was reversed by the incubation with bladder mucosal layer obtained from a donor WT mice, but not with the muscular layer. These findings clearly demonstrate 6-ND is the most potent endogenous relaxing agent of urinary bladder, and inhibition of its release is associated with bladder hyperreactivity.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"153 ","pages":"Pages 98-105"},"PeriodicalIF":3.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Generation and characterization of a conditional eNOS knock out mouse model for cell-specific reactivation of eNOS in gain-of-function studies 生成条件性 eNOS 基因敲除小鼠模型并确定其特征,以便在功能增益研究中对 eNOS 进行细胞特异性再激活。
IF 3.2 2区 生物学
Nitric oxide : biology and chemistry Pub Date : 2024-10-16 DOI: 10.1016/j.niox.2024.10.009
Anthea LoBue , Zhixin Li , Sophia K. Heuser , Junjie Li , Francesca Leo , Lukas Vornholz , Luke S. Dunaway , Tatsiana Suvorava , Brant E. Isakson , Miriam M. Cortese-Krott
{"title":"Generation and characterization of a conditional eNOS knock out mouse model for cell-specific reactivation of eNOS in gain-of-function studies","authors":"Anthea LoBue ,&nbsp;Zhixin Li ,&nbsp;Sophia K. Heuser ,&nbsp;Junjie Li ,&nbsp;Francesca Leo ,&nbsp;Lukas Vornholz ,&nbsp;Luke S. Dunaway ,&nbsp;Tatsiana Suvorava ,&nbsp;Brant E. Isakson ,&nbsp;Miriam M. Cortese-Krott","doi":"10.1016/j.niox.2024.10.009","DOIUrl":"10.1016/j.niox.2024.10.009","url":null,"abstract":"<div><div>Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) in the vessel wall regulates blood pressure and cardiovascular hemodynamics. In this study, we generated conditional eNOS knock out (KO) mice characterized by a duplicated/inverted exon 2 flanked with two pairs of loxP regions (eNOS<sup>inv/inv</sup>); a Cre-recombinase activity induces cell-specific reactivation of eNOS, as a result of a flipping of the inverted exon 2 (eNOS<sup>fl</sup>). This work aimed to test the efficiency of the Cre-mediated cell-specific recombination and the resulting eNOS expression/function. As proof of concept, we crossed eNOS<sup>inv/inv</sup> mice with DeleterCre<sup>pos</sup> (DelCre<sup>pos</sup>) mice, expressing Cre recombinase in all cells. We generated heterozygous eNOS<sup>fl/inv</sup> or homozygous eNOS<sup>fl/fl</sup> mice, and eNOS<sup>inv/inv</sup> littermate mice. We found that both eNOS<sup>fl/fl</sup> and eNOS<sup>fl/inv</sup> mice express eNOS and the overall expression level depends on the number of mutated alleles, while eNOS<sup>inv/inv</sup> mice did not show any eNOS expression. Vascular endothelial function was restored in eNOS<sup>fl/fl</sup> and eNOS<sup>fl/inv</sup> mice, as determined by ACh-dependent vasodilation of aortic rings. Cre-dependent reactivation of eNOS in eNOS<sup>fl/fl</sup> and eNOS<sup>fl/inv</sup> mice rescued eNOS<sup>inv/inv</sup> (phenotypically global eNOS KO) mice from hypertension. These findings demonstrate that eNOS expression is restored in eNOS<sup>fl/fl</sup> mice at comparable physiological levels of WT mice, and its functional activity is independent on the number of the reactivated alleles. Therefore, eNOS<sup>inv/inv</sup> mice are a useful model for studying the effects of conditional reactivation of eNOS and gene dosage effects in specific cells for gain-of-function studies.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"153 ","pages":"Pages 106-113"},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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