Angiotensin II-Induced Mesangial Cell Apoptosis: Role of Oxidative Stress

The increase of oxidative stress is one of the important characteristics of mammalian luteal regression. Previous investigations have revealed the essential role of reactive oxygen species (ROS) in luteal cell death during luteolysis, while it is unknown how ROS is regulated in this process. Considering the decrease of blood flow and increase of PGF2α during luteolysis, we hypothesized that the HIF-1α pathway may be involved in the regulation of ROS in the luteal cell of the late corpus luteum (CL). Here, by using a pseudopregnant rat model, we showed that the level of both HIF-1α and its downstream BNIP3 was increased during luteal regression. Consistently, we observed the increase of autophagy level during luteolysis, which is regulated in a Beclin1-independent manner. Comparing with early (Day 7 of pseudopregnancy) and middle CL (Day 14), the level of ROS was significantly increased in late CL, indicating the contribution of oxidative stress in luteolysis. Inhibition of HIF-1α by echinomycin (Ech), a potent HIF-1α inhibitor, ameliorated the upregulation of BNIP3 and NIX, as well as the induction of autophagy and the accumulation of ROS in luteal cells on Day 21 of pseudopregnancy. Morphologically, Ech treatment delayed the atrophy of the luteal structure at the late-luteal stage. An in vitro study indicated that inhibition of HIF-1α can also attenuate PGF2α-induced ROS and luteal cell apoptosis. Furthermore, the decrease of cell apoptosis can also be observed by ROS inhibition under PGF2α treatment. Taken together, our results indicated that HIF-1α signaling is involved in the regression of CL by modulating ROS production via orchestrating autophagy. Inhibition of HIF-1α could obviously hamper the apoptosis of luteal cells and the process of luteal regression.

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Higher Angiotensin II type 1 receptor (AT1R) levels and activity in the post-mortem brains of older persons with Alzheimer's disease

The Journals of Gerontology Series A ◽

10.1093/gerona/glab376 ◽

2021 ◽

Author(s):

Caglar Cosarderelioglu ◽

Lolita S Nidadavolu ◽

Claudene J George ◽

Ruth Marx ◽

Laura Powell ◽

...

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Amyloid Β ◽

Renin Angiotensin System ◽

Angiotensin Receptors ◽

Post Mortem ◽

Protein Levels ◽

Normal Individuals ◽

Markers Of Oxidative Stress

Abstract Aging is a key risk factor in Alzheimer's dementia (AD) development and progression. The primary dementia-protective benefits of Angiotensin II subtype 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, a brain-specific renin-angiotensin system (b-RAS) exists, which can be altered by AT1R blockers. Brain RAS acts mainly through three angiotensin receptors: AT1R, AT2R, and AT4R. Changes in these brain angiotensin receptors may accelerate the progression of AD. Using post-mortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n = 30) and AD patients (n = 30), we sought to dissect the b-RAS changes associated with AD and assess how these changes correlate with brain markers of oxidative stress, inflammation, and mitochondrial dysfunction as well as amyloid-β and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT1R and phospho-ERK (pERK) in the brains of AD participants. Brain AT1R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-β scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.

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T-2 Toxin-Induced Oxidative Stress Leads to Imbalance of Mitochondrial Fission and Fusion to Activate Cellular Apoptosis in the Human Liver 7702 Cell Line

Toxins ◽

10.3390/toxins12010043 ◽

2020 ◽

Vol 12 (1) ◽

pp. 43 ◽

Cited By ~ 5

Author(s):

Junhua Yang ◽

Wenbo Guo ◽

Jianhua Wang ◽

Xianli Yang ◽

Zhiqi Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Apoptosis ◽

Human Liver ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Mitochondrial Fusion ◽

Mitochondrial Dynamic ◽

Normal Human Liver ◽

Induced Apoptosis

T-2 toxin, as a highly toxic mycotoxin to humans and animals, induces oxidative stress and apoptosis in various cells and tissues. Apoptosis and mitochondrial fusion/fission are two tightly interconnected processes that are crucial for maintaining physiological homeostasis. However, the role of mitochondrial fusion/fission in apoptosis of T-2 toxin remains unknown. Hence, we aimed to explore the putative role of mitochondrial fusion/fission on T-2 toxin induced apoptosis in normal human liver (HL-7702) cells. T-2 toxin treatment (0, 0.1, 1.0, or 10 μg/L) for 24 h caused decreased cell viability and ATP concentration and increased production of (ROS), as seen by a loss of mitochondrial membrane potential (∆Ψm) and increase in mitochondrial fragmentation. Subsequently, the mitochondrial dynamic imbalance was activated, evidenced by a dose-dependent decrease and increase in the protein expression of mitochondrial fusion (OPA1, Mfn1, and Mfn2) and fission (Drp1 and Fis1), respectively. Furthermore, the T-2 toxin promoted the release of cytochrome c from mitochondria to cytoplasm and induced cell apoptosis triggered by upregulation of Bax and Bax/Bcl-2 ratios, and further activated the caspase pathways. Taken together, these results indicate that altered mitochondrial dynamics induced by oxidative stress with T-2 toxin exposure likely contribute to mitochondrial injury and HL-7702 cell apoptosis.

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ROLE OF CYCLOOXYGENASE-2 PATHWAY IN ANTI-OXIDATIVE EFFECT OF ASPIRIN AND IN ANGIOTENSIN II-INDUCED OXIDATIVE STRESS: PP.29.160

Journal of Hypertension ◽

10.1097/01.hjh.0000379698.14771.d8 ◽

2010 ◽

Vol 28 ◽

pp. e497

Author(s):

R Wu ◽

J de Champlain ◽

H Girouard

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Cyclooxygenase 2 ◽

Oxidative Effect

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Modulation of Gi Proteins in Hypertension: Role of Angiotensin II and Oxidative Stress

Current Cardiology Reviews ◽

10.2174/157340310793566046 ◽

2010 ◽

Vol 6 (4) ◽

pp. 298-308 ◽

Cited By ~ 8

Author(s):

Madhu B. Anand-Srivastava

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

And Oxidative Stress ◽

Gi Proteins

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Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy

Cell Death and Disease ◽

10.1038/s41419-019-2197-6 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 5

Author(s):

Qingqiang Xu ◽

Wenwen Shi ◽

Pan Lv ◽

Wenqi Meng ◽

Guanchao Mao ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Viability ◽

Aflatoxin B1 ◽

Cell Apoptosis ◽

Critical Role ◽

Hepatic Cell ◽

Hepatocellular Injury ◽

Caveolin 1 ◽

Induced Apoptosis

AbstractAflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

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