Influence of oxidative stress on inducing micturition dysfunction following chronic infravesical obstruction and the protective role of an antioxidant diet - association of in vivo and in vitro studies in rats

Hyperglycemia fluctuation is associated with diabetes mellitus (DM) complications when compared to persistent hyperglycemia. Previous studies have shown that paeoniflorin (PF), through its antiapoptosis, anti-inflammation, and antithrombotic properties, effectively protects against cardiovascular and cerebrovascular disease. However, the mechanism underlying the protection from PF against vascular injuries induced by hyperglycemia fluctuations remains poorly understood. Herein, we investigated the potential protective role of PF on human umbilical vein endothelial cells (HUVECs) subjected to intermittent glucose levels in vitro and in DM rats with fluctuating hyperglycemia in vivo. A remarkable increased apoptosis associated with elevated inflammation, increased oxidative stress, and high protein level of PKCβ1 was induced in HUVECs by intermittently changing glucose for 8 days, and PF recovered those detrimental changes. LY333531, a potent PKCβ1 inhibitor, and metformin manifested similar effects. Additionally, in DM rats with fluctuating hyperglycemia, PF protected against vascular damage as what has been observed in vitro. Taken together, PF attenuates the vascular injury induced by fluctuant hyperglycemia through oxidative stress inhibition, inflammatory reaction reduction, and PKCβ1 protein level repression, suggesting its perspective clinical usage.

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In Vivo and In Vitro Studies on Nickel Induced Reproductive Toxicity and the Protective Role of Melatonin.

Biology of Reproduction ◽

10.1093/biolreprod/83.s1.289 ◽

2010 ◽

Vol 83 (Suppl_1) ◽

pp. 289-289

Author(s):

Niraj R. Joshi ◽

Sudip Banerjee ◽

Raktim Mukherjee ◽

Shail Kumar Chaube ◽

T.G. Srivastava ◽

...

Keyword(s):

Reproductive Toxicity ◽

Protective Role ◽

In Vitro Studies

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Protective role of maize purple plant pigment against oxidative stress in fluorosis rat brain

Translational Neuroscience ◽

10.1515/tnsci-2020-0055 ◽

2020 ◽

Vol 11 (1) ◽

pp. 89-95

Author(s):

Boyan Li ◽

Keyana Nozzari Varkani ◽

Lu Sun ◽

Bo Zhou ◽

Xiaohong Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Rat Brain ◽

Neuronal Apoptosis ◽

Protective Role ◽

Fluoride Toxicity ◽

Plant Pigment

AbstractIn fluorosis-endemic areas, exposure to high levels of fluoride causes neurotoxicity such as lowered intelligence and cognitive impairment. Oxidative damage is critical to pathophysiologic processes of fluoride intoxication, and neurotoxicity of fluoride may be associated with oxidative stress. In previous studies, maize purple plant pigment (MPPP), which was rich in anthocyanins, showed a strong scavenging activity in vitro and in vivo. The present study aimed to determine whether treatment with MPPP can alleviate fluoride-induced oxidative damage in rat brain. After 3 months of experiment, brain tissues were assayed for oxidative stress variables, histological and Western blotting examinations. Our results showed that MPPP reduced the elevated malondialdehyde levels, increased superoxide dismutase activity, and further attenuated histopathological alterations and mitigated neuronal apoptosis. Importantly, MPPP also reversed changes in Bax and Bcl-2. Therefore, it was speculated that MPPP protects brain tissue from fluoride toxicity through its antioxidant capacity.

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Oxidative stress promotes liver cancer metastasis via a PKA-activated RNF25/ECAD/YAP circuit

10.21203/rs.3.rs-1197819/v1 ◽

2022 ◽

Author(s):

Zhao Huang ◽

Li Zhou ◽

Jiufei Duan ◽

Siyuan Qin ◽

Yu Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Cancer Metastasis ◽

Anoikis Resistance ◽

Antioxidant Genes ◽

Redox Sensor ◽

Stress Signals ◽

Hcc Cells

Abstract Loss of E-cadherin (ECAD), often caused by epigenetic inactivation, is closely associated with tumor metastasis. However, how ECAD is regulated in response to oxidative stress during tumorigenesis is largely unknown. Here we identify RNF25 as a new E3 ligase of ECAD, whose activation by oxidative stress leads to ECAD protein degradation in hepatocellular carcinoma (HCC). Loss of ECAD activates YAP, which in turn promotes the transcription of RNF25, thus forming a positive feedback loop to sustain the ECAD downregulation. YAP activation mitigates oxidative stress in detached HCC cells by upregulating antioxidant genes, protecting detached HCC cells from ferroptosis, resulting in anoikis resistance. Mechanistically, we found that protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344, which increases its kinase activity towards RNF25 phosphorylation at Ser450, facilitating RNF25-mediated degradation of ECAD. Moreover, RNF25 expression is associated with HCC metastasis and depletion of RNF25 is sufficient to diminish HCC invasion and metastasis in vitro and in vivo. Together, these results identify a dual role of RNF25 as a critical regulator of ECAD protein turnover, promoting both anoikis resistance and metastasis, and PKA is a necessary redox sensor to enable this process. Our study provides mechanistic insight into how tumor cells sense oxidative stress signals to spread while escaping cell death.

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A critical role of VLA-4 in erythropoiesis in vivo

Blood ◽

10.1182/blood.v87.6.2513.bloodjournal8762513 ◽

1996 ◽

Vol 87 (6) ◽

pp. 2513-2517 ◽

Cited By ~ 54

Author(s):

K Hamamura ◽

H Matsuda ◽

Y Takeuchi ◽

S Habu ◽

H Yagita ◽

...

Keyword(s):

Monoclonal Antibody ◽

Fetal Liver ◽

Critical Role ◽

In Utero ◽

In Vitro Studies ◽

Specific Interactions ◽

Erythroid Progenitors

Hematopoiesis requires specific interactions with the microenvironments, and VLA-4 has been implicated in these interactions based on in vitro studies. To study the role of VLA-4 in hematopoiesis in vivo, we performed in utero treatment of mice with an anti-VLA-4 monoclonal antibody. Although all hematopoietic cells in fetal liver expressed VLA-4, the treatment specifically induced anemia. It had no effect on the development of nonerythroid lineage cells, including lymphoids and myeloids. In the treated liver almost no erythroblast was detected, whereas the erythroid progenitors, which give rise to erythroid colonies in vitro, were present. These results indicate that VLA-4 plays a critical role in erythropoiesis, while it is not critical in lymphopoiesis in vivo.

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HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00143.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. L269-L279 ◽

Cited By ~ 4

Author(s):

Tianwen Lai ◽

Mindan Wu ◽

Chao Zhang ◽

Luanqing Che ◽

Feng Xu ◽

...

Keyword(s):

Airway Inflammation ◽

Inflammatory Cytokines ◽

Allergic Inflammation ◽

Allergic Airway Inflammation ◽

Inflammatory Cells ◽

Protective Role ◽

In Vivo Models

Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/− mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/− mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation.

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Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPKα Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7901735 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Yan-Yan Meng ◽

Yu-Pei Yuan ◽

Xin Zhang ◽

Chun-Yan Kong ◽

Peng Song ◽

...

Keyword(s):

Oxidative Stress ◽

Therapeutic Potential ◽

Cell Loss ◽

Protective Role ◽

Protective Effects ◽

Morphological Examination ◽

Heart Injury ◽

Amp Activated Protein Kinase

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase α (AMPKα) in vivo and in vitro. Moreover, inhibition of AMPKα could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPKα. GE has therapeutic potential for the treatment of DOX cardiotoxicity.

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Protective Effects of Dietary Antioxidants against Vanadium-Induced Toxicity: A Review

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1490316 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 5

Author(s):

Iwona Zwolak

Keyword(s):

Oxidative Stress ◽

Animal Studies ◽

Toxic Metal ◽

Protective Effects ◽

Dietary Antioxidants ◽

Vanadium Toxicity ◽

Preventive Effects

Vanadium (V) in its inorganic forms is a toxic metal and a potent environmental and occupational pollutant and has been reported to induce toxic effects in animals and people. In vivo and in vitro data show that high levels of reactive oxygen species are often implicated in vanadium deleterious effects. Since many dietary (exogenous) antioxidants are known to upregulate the intrinsic antioxidant system and ameliorate oxidative stress-related disorders, this review evaluates their effectiveness in the treatment of vanadium-induced toxicity. Collected data, mostly from animal studies, suggest that dietary antioxidants including ascorbic acid, vitamin E, polyphenols, phytosterols, and extracts from medicinal plants can bring a beneficial effect in vanadium toxicity. These findings show potential preventive effects of dietary antioxidants on vanadium-induced oxidative stress, DNA damage, neurotoxicity, testicular toxicity, and kidney damage. The relevant mechanistic insights of these events are discussed. In summary, the results of studies on the role of dietary antioxidants in vanadium toxicology appear encouraging enough to merit further investigations.

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The role of BH3-only protein Bim extends beyond inhibiting Bcl-2–like prosurvival proteins

The Journal of Cell Biology ◽

10.1083/jcb.200905153 ◽

2009 ◽

Vol 186 (3) ◽

pp. 355-362 ◽

Cited By ~ 131

Author(s):

Delphine Mérino ◽

Maybelline Giam ◽

Peter D. Hughes ◽

Owen M. Siggs ◽

Klaus Heger ◽

...

Keyword(s):

Family Members ◽

Binding Specificity ◽

In Vitro Studies ◽

Genetic Approach ◽

Activation Model ◽

Bh3 Domain ◽

Indirect Activation

Proteins of the Bcl-2 family are critical regulators of apoptosis, but how its BH3-only members activate the essential effectors Bax and Bak remains controversial. The indirect activation model suggests that they simply must neutralize all of the prosurvival Bcl-2 family members, whereas the direct activation model proposes that Bim and Bid must activate Bax and Bak directly. As numerous in vitro studies have not resolved this issue, we have investigated Bim's activity in vivo by a genetic approach. Because the BH3 domain determines binding specificity for Bcl-2 relatives, we generated mice having the Bim BH3 domain replaced by that of Bad, Noxa, or Puma. The mutants bound the expected subsets of prosurvival relatives but lost interaction with Bax. Analysis of the mice showed that Bim's proapoptotic activity is not solely caused by its ability to engage its prosurvival relatives or solely to its binding to Bax. Thus, initiation of apoptosis in vivo appears to require features of both models.

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