scholarly journals MKRN1 Ubiquitylates p21 to Protect against Intermittent Hypoxia-Induced Myocardial Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xue Bai ◽  
Hui Yang ◽  
Jiayuan Pu ◽  
Yan Zhao ◽  
Ying Jin ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Western Blot ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Sleep Apnea Syndrome ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Myocardial Apoptosis ◽  
Protein Ubiquitination ◽  
Obstructive Sleep

Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.

Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1

2012 ◽  
Vol 303 (11) ◽  
pp. R1175-R1185 ◽  
Author(s):  
Mei-Ya Shen ◽  
Ya-Ling Luo ◽  
Chung-Huan Yang ◽  
Ting Ruan ◽  
Ching Jung Lai
Keyword(s):  
Reactive Oxygen Species ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Electrophysiological Study ◽  
Reactive Oxygen ◽  
Vagal Afferents ◽  
Radical Scavenger ◽  
Oxygen Species ◽  
C Fibers ◽  
Obstructive Sleep

Obstructive sleep apnea, manifested by intermittent hypoxia and excess production of reactive oxygen species (ROS) in airways, is associated with hyperreactive airway diseases, but the mechanism remains unclear. Sensitization of lung vagal C fibers (LVCFs) contributes to the airway hypersensitivity. We investigated the mechanisms underlying the sensitization of LVCFs with acute intermittent hypoxia (AIH), by 10 episodes of exposure to 30 s of hypoxic air (0%, 5%, or 10% O2) followed by 30 s of room air in anesthetized, open-chest, and artificially ventilated rats. Reflex apneic response to intravenous capsaicin (an LVCF stimulant), as measured by phrenic nerve activity, was concentration dependently augmented by AIH. Similarly, reflex apneic response to intravenous α,β-methylene-ATP (another LVCF stimulant) was augmented by AIH (0% O2). The reflex apnea evoked by these two stimulants was abolished by bilateral vagotomy, which suggests the involvement of lung vagal afferents. The AIH-augmented apneic response to these two stimulants was prevented by pretreatment with dimethylthiourea (a hydroxyl radical scavenger), N-acetyl-l-cysteine (an antioxidant) and HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist]. Consistently, electrophysiological study revealed the afferent responses of LVCFs to capsaicin or α,β-methylene-ATP were augmented by AIH, and this sensitization of LVCFs was prevented by dimethylthiourea, N-acetyl-l-cysteine, and HC-030031. In contrast, AIH did not alter the afferent response of LVCFs to mechanical stimulation by lung hyperinflation. We concluded that AIH sensitizes LVCFs in rats, thus resulting in exaggerated airway reflexogenic responses to chemical stimulants, possibly by ROS action and activation of TRPA1 receptors.

Respiratory plasticity following intermittent hypoxia: roles of protein phosphatases and reactive oxygen species

2007 ◽  
Vol 35 (5) ◽  
pp. 1269-1272 ◽  
Author(s):  
J.E.R. Wilkerson ◽  
P.M. MacFarlane ◽  
M.S. Hoffman ◽  
G.S. Mitchell
Keyword(s):  
Reactive Oxygen Species ◽  
Motor Neurons ◽  
Intermittent Hypoxia ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Obstructive Sleep ◽  
Cord Injury ◽  
Respiratory Plasticity ◽  
Sustained Hypoxia ◽  
Synaptic Mechanisms

Plasticity is an important property of the respiratory control system. One of the best-studied models of respiratory plasticity is pLTF (phrenic long-term facilitation). pLTF is a progressive increase in phrenic motor output lasting several hours following acute exposure to intermittent hypoxia. Similar to many other forms of neuroplasticity, pLTF is pattern-sensitive; it is induced by intermittent, but not sustained hypoxia of similar cumulative duration. Our understanding of the cellular/synaptic mechanisms underlying pLTF has increased considerably in recent years. Here, we review accumulating evidence suggesting that the pattern-sensitivity of pLTF arises substantially from differential reactive oxygen species formation and subsequent protein phosphatase inhibition during intermittent compared with sustained hypoxia in or near phrenic motor neurons. A detailed understanding of the cellular/synaptic mechanisms of pLTF may provide the rationale for new pharmacological approaches in the treatment of severe ventilatory control disorders, such as obstructive sleep apnoea and respiratory insufficiency either following spinal cord injury or during neurodegenerative diseases such as amyotrophic lateral sclerosis.

A Novel pH-responsive Fe-MOF System for Enhanced Cancer Treatment Mediated by Fenton Reaction

2021 ◽  
Author(s):  
Senlin Wang ◽  
Hong-Shuai Wu ◽  
Kai Sun ◽  
Jinzhong Hu ◽  
Fanghui Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydroxyl Radical ◽  
Cancer Treatment ◽  
Cell Apoptosis ◽  
Fenton Reaction ◽  
Reactive Oxygen ◽  
Cationic Polymer ◽  
Intracellular Reactive Oxygen Species ◽  
Oxygen Species ◽  
Ph Responsive

Recently, the toxic hydroxyl radical (·OH) has received wide interest in inducing cell apoptosis by increasing the intracellular reactive oxygen species (ROS) levels. Herein, a cationic polymer (MV-PAH) was rationally...

Protective Effects of Crataegus pinnatifida Extracts and Crataegolic Acid Against Neurotoxicity of Paraquat in PC12 Cells

2021 ◽  
Vol 20 (1) ◽  
pp. 76-83
Author(s):  
Chi-Sen Chang ◽  
Yuh-Chiang Shen ◽  
Chi-Wen Juan ◽  
Chia-Lin Chang ◽  
Po-Kai Lin
Keyword(s):  
Reactive Oxygen Species ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Active Component ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
B Cell Lymphoma ◽  
Oxygen Species ◽  
Protein Levels ◽  
Crataegus Pinnatifida

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

Reactive oxygen species-mediated caspase-3 pathway involved in cell apoptosis of Karenia mikimotoi induced by linoleic acid

2018 ◽  
Vol 36 ◽  
pp. 48-56 ◽  
Author(s):  
Meiaoxue Han ◽  
Renjun Wang ◽  
Ning Ding ◽  
Xiuxia Liu ◽  
Ningning Zheng ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Linoleic Acid ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Karenia Mikimotoi

Trivalent methylated arsenic metabolites induce apoptosis in human myeloid leukemic HL-60 cells through generation of reactive oxygen species

Metallomics ◽  
2014 ◽  
Vol 6 (8) ◽  
pp. 1502-1512 ◽  
Author(s):  
Kanwal Rehman ◽  
Yu Jie Fu ◽  
Yan Fang Zhang ◽  
Qian Qian Wang ◽  
Bin Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Apoptosis ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Trivalent Arsenic ◽  
Arsenic Metabolites

Trivalent arsenic metabolites mediate HL-60 cell apoptosis via ROS.

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