Abstract
Cardiovascular diseases (CVDs) are a group of disorders that affect the heart and blood vessels. Due to their multifactorial nature and wide variation, CVDs are the leading cause of death worldwide. Understanding the molecular alterations leading to the development of heart and vessel pathologies is crucial for successfully treating and preventing CVDs. One of the causative factors of CVD etiology and progression is acute oxidative stress, a toxic condition characterized by elevated intracellular levels of reactive oxygen species (ROS). Left unabated, ROS can damage virtually any cellular component and affect essential biological processes, including protein synthesis. Defective or insufficient protein translation results in production of faulty protein products and disturbances of protein homeostasis, thus promoting pathologies. The relationships between translational dysregulation, ROS, and cardiovascular disorders will be examined in this review.
Highlights
The process of protein synthesis, or protein translation, constitutes the last and final step of the central dogma of molecular biology: assembly of polypeptides based on the information encoded by mRNAs
The analysis revealed extensive fragmentation of mature 18S and 28S rRNAs in cells derived from plaques, while ribosomes purified from control arteries contained intact rRNA species
In addition to directly regulating gene expression by acting on the components of the protein synthesis machinery, oxidative stress can alter gene expression via small noncoding microRNAs. miRNAs, on average 22 nucleotides in length, are transcribed as precursors and processed into mature miRNAs capable of interacting with target cellular mRNA transcripts; in most cases, miRNAs induce target degradation (Figure 2D). miRNAs are critical for normal animal development by fine-tuning gene expression, while abnormalities in miRNA expression are associated with many human diseases
Summary
The process of protein synthesis, or protein translation, constitutes the last and final step of the central dogma of molecular biology: assembly of polypeptides based on the information encoded by mRNAs. ROS is a common name for diverse chemical species, including superoxide anions, hydrogen peroxide, hypochlorous acid, nitric oxide, peroxynitrite, singlet oxygen, hydroperoxyl, and the hydroxyl radicals (Table 1), that are produced in cells as by-products of normal cellular metabolism Each of these molecules has its own unique characteristics, such as way of inactivation, substrate preferences, reactivity, kinetics, diffusion properties, etc. XO can transfer electrons to molecular oxygen, resulting in the formation of superoxide during xanthine or hypoxanthine oxidation and promoting further heart damage [16] Another example of enzymes that supply ROS is NADPH oxidases (NOXs), a unique family of enzymes the only function of which is producing ROS. NOXs are implicated in CVD pathologies, including myocardial ischemia-reperfusion injuries, myocardial damage, and cardiomyocyte death [18,19]
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