Mitochondrial Aldehyde Dehydrogenase, A Potential Drug Target for Protection of Heart and Brain from Ischemia/Reperfusion Injury

2014 ◽  
Vol 15 (10) ◽  
pp. 948-955 ◽  
Author(s):  
Xiu-Ju Luo ◽  
Bin Liu ◽  
Qi-Lin Ma ◽  
Jun Peng
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Drug Target ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Beneficial Effects ◽  
Therapeutic Value

Mitochondrial aldehyde dehydrogenase (ALDH2) is an isoenzyme of aldehyde dehydrogenases (ALDH), a group of enzymes that are responsible for clearance of aldehydes in the body. In animal myocardial or cerebral ischemia/ reperfusion (I/R) models, accumulation of toxic aldehydes, such as 4-hydroxy-2-nonenal and malondialdehyde, is thought to be an important mechanism for myocardial and cerebral I/R injury. Among the isoenzymes of ALDH, ALDH2 is believed to play a major role in clearance of toxic aldehydes. Thus, ALDH2 might be a potential drug target for protection of the heart or brain from I/R injury. Indeed, some of the newly identified ALDH2 activators (such as Alda-1) have demonstrated beneficial effects on heart and brain I/R injury. In addition, ALDH activity is present at high levels in some stem or progenitor cells, known as ALDH bright (ALDHbr) cells, which possess potential value in treating patients with myocardial ischemia. The main purpose of this review is 1) to summarize recent findings regarding the role of ALDH2 in protection of heart or brain from I/R injury, 2) to list the available ALDH2 activators with their potency, selectivity and clinical potentials, and 3) to provide a rationale for ALDHbr cells in clinical therapeutic value.

scholarly journals Activity-based protein profiling reveals deubiquitinase and aldehyde dehydrogenase targets of a cyanopyrrolidine probe

2021 ◽  
Author(s):  
Nattawadee Panyain ◽  
Aurélien Godinat ◽  
Aditya Raymond Thawani ◽  
Sofía Lachiondo-Ortega ◽  
Katie Mason ◽  
...  
Keyword(s):  
Aldehyde Dehydrogenase ◽  
Lung Fibrosis ◽  
Drug Target ◽  
Protein Profiling ◽  
Deubiquitinating Enzyme ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Bona Fide ◽  
Carboxy Terminal

Ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme (DUB), is a potential drug target in various cancers, and liver and lung fibrosis. However, bona fide functions and substrates of UCHL1...

scholarly journals Role of aldehyde dehydrogenase 2 in ischemia reperfusion injury: An update

2018 ◽  
Vol 24 (27) ◽  
pp. 2984-2994 ◽  
Author(s):  
Arnau Panisello-Roselló ◽  
Alexandre Lopez ◽  
Emma Folch-Puy ◽  
Teresa Carbonell ◽  
Anabela Rolo ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Aldehyde Dehydrogenase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Aldehyde Dehydrogenase 2

scholarly journals Sulphurous Mineral Waters: New Applications for Health

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jose Manuel Carbajo ◽  
Francisco Maraver
Keyword(s):  
Hydrogen Sulphide ◽  
Mineral Water ◽  
Ischemia Reperfusion Injury ◽  
Inflammatory Diseases ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Mineral Waters ◽  
Beneficial Effects ◽  
Low Levels ◽  
New Applications

Sulphurous mineral waters have been traditionally used in medical hydrology as treatment for skin, respiratory, and musculoskeletal disorders. However, driven by recent intense research efforts, topical treatments are starting to show benefits for pulmonary hypertension, arterial hypertension, atherosclerosis, ischemia-reperfusion injury, heart failure, peptic ulcer, and acute and chronic inflammatory diseases. The beneficial effects of sulphurous mineral waters, sulphurous mud, or peloids made from sulphurous mineral water have been attributed to the presence of sulphur mainly in the form of hydrogen sulphide. This form is largely available in conditions of low pH when oxygen concentrations are also low. In the organism, small amounts of hydrogen sulphide are produced by some cells where they have numerous biological signalling functions. While high levels of hydrogen sulphide are extremely toxic, enzymes in the body are capable of detoxifying it by oxidation to harmless sulphate. Hence, low levels of hydrogen sulphide may be tolerated indefinitely. In this paper, we review the chemistry and actions of hydrogen sulphide in sulphurous mineral waters and its natural role in body physiology. This is followed by an update of available data on the impacts of exogenous hydrogen sulphide on the skin and internal cells and organs including new therapeutic possibilities of sulphurous mineral waters and their peloids.

scholarly journals The role of mitochondria in cellular toxicity as a potential drug target

2018 ◽  
Vol 34 (2) ◽  
pp. 87-91 ◽  
Author(s):  
Duojiao Wu ◽  
Xiangdong Wang ◽  
Hongzhi Sun
Keyword(s):  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Cellular Toxicity

scholarly journals Role of Hydrogen Sulfide in the Endocrine System

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao-Jie Chen ◽  
Ebenezeri Erasto Ngowi ◽  
Lei Qian ◽  
Tao Li ◽  
Yang-Zhe Qin ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Endocrine System ◽  
The Body ◽  
Endocrine Disorders ◽  
Hormone Concentration ◽  
Treatment Of Hypertension ◽  
Anti Inflammation

Hydrogen sulfide (H2S), as one of the three known gaseous signal transduction molecules in organisms, has attracted a surging amount of attention. H2S is involved in a variety of physiological and pathological processes in the body, such as dilating blood vessels (regulating blood pressure), protecting tissue from ischemia-reperfusion injury, anti-inflammation, carcinogenesis, or inhibition of cancer, as well as acting on the hypothalamus and pancreas to regulate hormonal metabolism. The change of H2S concentration is related to a variety of endocrine disorders, and the change of hormone concentration also affects the synthesis of H2S. Understanding the effect of biosynthesis and the concentration of H2S on the endocrine system is useful to develop drugs for the treatment of hypertension, diabetes, and other diseases.

scholarly journals The Role of Indoleamine 2,3 Dioxygenase in Beneficial Effects of Stem Cells in Hind Limb Ischemia Reperfusion Injury

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e95720 ◽  
Author(s):  
Mohamad Masoumy ◽  
Jack Yu ◽  
Jun Yao Liu ◽  
Nathan Yanasak ◽  
Christopher Middleton ◽  
...  
Keyword(s):  
Stem Cells ◽  
Reperfusion Injury ◽  
Hind Limb ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Hind Limb Ischemia ◽  
Beneficial Effects ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1055 ◽  
Author(s):  
Yang ◽  
Wu ◽  
Yen ◽  
Liu ◽  
Hwang ◽  
...  
Keyword(s):  
Drug Target ◽  
Redox Homeostasis ◽  
Redox Signaling ◽  
G6pd Activity ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Cellular Processes ◽  
Reducing Equivalent ◽  
Glucose 6 Phosphate Dehydrogenase

The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.

STAT3: A Potential Drug Target for Tumor and Inflammation

2019 ◽  
Vol 19 (15) ◽  
pp. 1305-1317 ◽  
Author(s):  
Yang Sheng Hu ◽  
Xu Han ◽  
Xin Hua Liu
Keyword(s):  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Normal Cells ◽  
Signal Transducers ◽  
Current State ◽  
Cellular Signal ◽  
State Of Research ◽  
Sustained Activation

STAT (Signal Transducers and Activators of Transcription) is a cellular signal transcription factor involved in the regulation of many cellular activities, such as cell differentiation, proliferation, angiogenesis in normal cells. During the study of the STAT family, STAT3 was found to be involved in many diseases, such as high expression and sustained activation of STAT3 in tumor cells, promoting tumor growth and proliferation. In the study of inflammation, it was found that it plays an important role in the anti-inflammatory and repairing of damage tissues. Because of the important role of STAT3, a large number of studies have been obtained. At the same time, after more than 20 years of development, STAT3 has also been used as a target for drug therapy. And the discovery of small molecule inhibitors also promoted the study of STAT3. Since STAT3 has been extensively studied in inflammation and tumor regulation, this review presents the current state of research on STAT3.

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