Protective effect of HDL on NADPH oxidase-derived super oxide anion mediates hypoxia-induced cardiomyocyte apoptosis

Su, Wen; Tamilselvi, Shanmugam; Shen, Chia Yao; Day, Cecilia Hsuan; Chun, Li Chin; Cheng, Li Yi; Ou, Hsiu Chung; Chen, Ray Jade; Viswanadha, Vijaya Padma; Kuo, Wei Wen; Huang, Chih‐Yang

doi:10.1371/journal.pone.0179492

Cited by 10 publications

(10 citation statements)

References 39 publications

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“…During the hypoxic condition, down regulation of the survival protein,p‐AKTser473 and anti‐apoptotic protein BCL2 with upregulation of pro‐apoptotic proteins, Bax and caspase‐3 expressions promote apoptosis of cardiac cells. It has been found that NOX mediated ROS is responsible for apoptosis in cardiomyocytes under hypoxia conditions through AT1 and PKC activation 53 . Obstructive sleep apnea (OSA) mediated chronic intermittent hypoxia (CIH) is also involved in NOX‐2 mediated ROS generation 54 .…”

Section: Human Pathologies and Nox Connectionsmentioning

confidence: 99%

Molecular insights of NADPH oxidases and its pathological consequences

Waghela

Vaidya

Agrawal

et al. 2020

Cell Biochemistry & Function

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Reactive oxygen species (ROS), formed by the partial reduction of oxygen, were for a long time considered to be a byproduct of cellular metabolism. Since, increase in cellular levels of ROS results in oxidative stress leading to damage of nucleic acids, proteins, and lipids resulting in numerous pathological conditions; ROS was considered a bane for aerobic species. Hence, the discovery of NADPH oxidases (NOX), an enzyme family that specifically generates ROS as its prime product came as a surprise to redox biologists. NOX family proteins participate in various cellular functions including cell proliferation and differentiation, regulation of genes and protein expression, apoptosis, and host defence immunological response. Balanced expression and activation of NOX with subsequent production of ROS are critically important to regulate various genes and proteins to maintain homeostasis of the cell. However, dysregulation of NOX activation leading to enhanced ROS levels is associated with various pathophysiologies including diabetes, cardiovascular diseases, neurodegenerative diseases, ageing, atherosclerosis, and cancer. Although our current knowledge on NOX signifies its importance in the normal functioning of various cellular pathways; yet the choice of ROS producing enzymes which can tip the scale from homeostasis toward damage, as mediators of biological functions remain an oddity. Though the role of NOX in maintaining normal cellular functions is now deemed essential, yet its dysregulation leading to catastrophic events cannot be denied. Hence, this review focuses on the involvement of NOX enzymes in various pathological conditions imploring them as possible targets for therapies. Significance of the study The NOXs are multi‐subunit enzymes that generate ROS as a prime product. NOX generated ROS are usually regulated by various molecular factors and play a vital role in different physiological processes. The dysregulation of NOX activity is associated with pathological consequences. Recently, the dynamic proximity of NOX enzymes with different molecular signatures of pathologies has been studied extensively. It is essential to identify the precise role of NOX machinery in its niche during the progression of pathology. Although inhibition of NOX could be a promising approach for therapeutic interventions, it is critical to expand the current understanding of NOX's dynamicity and shed light on their molecular partners and regulators.

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Section: Human Pathologies and Nox Connectionsmentioning

confidence: 99%

Molecular insights of NADPH oxidases and its pathological consequences

Waghela

Vaidya

Agrawal

et al. 2020

Cell Biochemistry & Function

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“…Severe hypoxic environmental condition dramatically appeared after ACL injury is generally considered as a major reason leading to the difficulty of ACL repair due to its adverse regulatory effects on matrix metalloproteinase 2 expression levels (Wang et al, ). What’s more, numbers of studies confirmed that severe hypoxia was harmful to the cell survival, such as cardiomyocyte (Wen et al, ), osteoblasts (Ma et al, ), or giloma cell (Brucker, Maurer, Harter, Rieger, & Steinbach, ). Besides, it was indicated that some ligament cells or tenocytes would undergo a hypoxic environmental condition after injury and cell apoptosis was induced (Aukkarasongsup, Haruyama, Matsumoto, Shiga, & Moriyama, ; Millar et al, ; Song, Zhou, Shu, & Ni, ).…”

Section: Introductionmentioning

confidence: 97%

MGF E peptide improves anterior cruciate ligament repair by inhibiting hypoxia‐induced cell apoptosis and accelerating angiogenesis

Sha

Yang

2018

Journal Cellular Physiology

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Severe hypoxic microenvironment endangers cell survival of anterior cruciate ligament (ACL) fibroblasts and is harmful to ACL repair and regeneration. In the current study, we explored the effects of mechanogrowth factor (MGF) E peptide on the hypoxia‐induced apoptosis of ACL fibroblasts and relevant mechanisms. It demonstrated that severe hypoxia promoted hypoxia‐inducible factor‐1α (HIF‐1α) expression and caused cell apoptosis of ACL fibroblasts through increasing caspase 3/7/9 messenger RNA (mRNA), cleaved caspase 3 and proapoptotic proteins expression levels but decreasing antiapoptotic proteins expression levels. Fortunately, MGF E peptide effectively protected ACL fibroblasts against hypoxia‐induced apoptosis through regulating caspase 3/7/9 mRNA, cleaved caspase 3 and apoptosis‐relevant proteins expression levels. Simultaneously, mitochondrial, @@@MEK‐ERK1/2 (extracellular‐signal‐regulated kinase 1/2), and phosphoinositide‐3‐kinase‐protein kinase B (PI3K‐Akt) pathways were involved in MGF E peptide regulating hypoxia‐induced apoptosis of ACL fibroblasts. In rabbit ACL rupture model, MGF E peptide also decreased HIF‐1α expression levels, cell apoptosis, and facilitated cell proliferation. In addition, MGF could accelerate angiogenesis after ACL injury probably owing to its recruitment of proangiogenesis cells by stromal cell‐derived factor 1α/CXCR4 axis and stimulation of vascular endothelial growth factor α expression level. In conclusion, our findings suggested that MGF E peptide could be utilized for ACL repair and regeneration and supplied experimental support for its application in clinical ACL treatment as a potential strategy.

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“…heart failure) [46,47]. Cardiorenal "connectors" such as erythrocyte superoxide dismutase (SOD1), GSH, and NADPH have also been used to measure kidney and heart injury [48][49][50][51][52][53].…”

Section: Oxidative Stressmentioning

confidence: 99%

New insights into the pathophysiological mechanisms underlying cardiorenal syndrome

Wang

Zhang

et al. 2020

Aging

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Communication between the heart and kidney occurs through various bidirectional pathways. The heart maintains continuous blood flow through the kidney while the kidney regulates blood volume thereby allowing the heart to pump effectively. Cardiorenal syndrome (CRS) is a pathologic condition in which acute or chronic dysfunction of the heart or kidney induces acute or chronic dysfunction of the other organ. CRS type 3 (CRS-3) is defined as acute kidney injury (AKI)-mediated cardiac dysfunction. AKI is common among critically ill patients and correlates with increased mortality and morbidity. Acute cardiac dysfunction has been observed in over 50% of patients with severe AKI and results in poorer clinical outcomes than heart or renal dysfunction alone. In this review, we describe the pathophysiological mechanisms responsible for AKI-induced cardiac dysfunction. Additionally, we discuss current approaches in the management of patients with CRS-3 and the development of targeted therapeutics. Finally, we summarize current challenges in diagnosing mild cardiac dysfunction following AKI and in understanding CRS-3 etiology.

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Protective effect of HDL on NADPH oxidase-derived super oxide anion mediates hypoxia-induced cardiomyocyte apoptosis

Cited by 10 publications

References 39 publications

Molecular insights of NADPH oxidases and its pathological consequences

Molecular insights of NADPH oxidases and its pathological consequences

MGF E peptide improves anterior cruciate ligament repair by inhibiting hypoxia‐induced cell apoptosis and accelerating angiogenesis

New insights into the pathophysiological mechanisms underlying cardiorenal syndrome

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