The Expression of Genes , , and in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.

Background: It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.

Kynurenic Acid/AhR Signaling at the Junction of Inflammation and Cardiovascular Diseases.

Persistent systemic chronic inflammatory conditions are linked with many pathologies, including cardiovascular diseases (CVDs), a leading cause of death across the globe. Among various risk factors, one of the new possible contributors to CVDs is the metabolism of essential amino acid tryptophan. Proinflammatory signals promote tryptophan metabolism via the kynurenine (KYN) pathway (KP), thereby resulting in the biosynthesis of several immunomodulatory metabolites whose biological effects are associated with the development of symptoms and progression of various inflammatory diseases.

AhR and HIF-1 Signaling Pathways in Benign Meningioma under Hypoxia.

The role of hypoxia in benign meningiomas is less clear than that in the malignant meningiomas. Hypoxia-induced transcription factor 1 subunit alpha (HIF-1) and its downstream signaling pathways play a central role in the mechanism of hypoxia. HIF-1 forms a complex with the aryl hydrocarbon receptor nuclear translocator (ARNT) protein and can compete for ARNT with aryl hydrocarbon receptor (AhR).

AhR and Wnt/β-Catenin Signaling Pathways and Their Interplay.

As evolutionarily conserved signaling cascades, AhR and Wnt signaling pathways play a critical role in the control over numerous vital embryonic and somatic processes. AhR performs many endogenous functions by integrating its signaling pathway into organ homeostasis and into the maintenance of crucial cellular functions and biological processes. The Wnt signaling pathway regulates cell proliferation, differentiation, and many other phenomena, and this regulation is important for embryonic development and the dynamic balance of adult tissues.

The Role of CYP3A in Health and Disease.

CYP3A is an enzyme subfamily in the cytochrome P450 (CYP) superfamily and includes isoforms CYP3A4, CYP3A5, CYP3A7, and CYP3A43. CYP3A enzymes are indiscriminate toward substrates and are unique in that these enzymes metabolize both endogenous compounds and diverse xenobiotics (including drugs); almost the only common characteristic of these compounds is lipophilicity and a relatively large molecular weight. CYP3A enzymes are widely expressed in human organs and tissues, and consequences of these enzymes' activities play a major role both in normal regulation of physiological levels of endogenous compounds and in various pathological conditions.

Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance.

The aryl hydrocarbon receptor (AhR) has long been implicated in the induction of a battery of genes involved in the metabolism of xenobiotics and endogenous compounds. AhR is a ligand-activated transcription factor necessary for the launch of transcriptional responses important in health and disease. In past decades, evidence has accumulated that AhR is associated with the cellular response to oxidative stress, and this property of AhR must be taken into account during investigations into a mechanism of action of xenobiotics that is able to activate AhR or that is susceptible to metabolic activation by enzymes encoded by the genes that are under the control of AhR.

The Role of Aryl Hydrocarbon Receptor (AhR) in Brain Tumors.

Primary brain tumors, both malignant and benign, are diagnosed in adults at an incidence rate of approximately 23 people per 100 thousand. The role of AhR in carcinogenesis has been a subject of debate, given that this protein may act as either an oncogenic protein or a tumor suppressor in different cell types and contexts. Lately, there is growing evidence that aryl hydrocarbon receptor (AhR) plays an important part in the development of brain tumors.

Menadione Suppresses Benzo(α)pyrene-Induced Activation of Cytochromes P450 1A: Insights into a Possible Molecular Mechanism.

Oxidative reactions that are catalyzed by cytochromes P450 1A (CYP1A) lead to formation of carcinogenic derivatives of arylamines and polycyclic aromatic hydrocarbons (PAHs), such as the widespread environmental pollutant benzo(α)pyrene (BP). These compounds upregulate CYP1A at the transcriptional level via an arylhydrocarbon receptor (AhR)-dependent signaling pathway. Because of the involvement of AhR-dependent genes in chemically induced carcinogenesis, suppression of this signaling pathway could prevent tumor formation and/or progression.

Molecular mechanisms of cold-induced CYP1A activation in rat liver microsomes.

Cytochrome P4501A (the CYP1A1 and CYP1A2 enzymes) is known to metabolize anthropogenic xenobiotics to carcinogenic and mutagenic compounds. CYP1A1 transcriptional activation is regulated via the aryl hydrocarbon receptor (AhR)-dependent signal transduction pathway. CYP1A2 activation may occur through the AhR-dependent or AhR-independent signal transduction pathways.