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Oxidative stress and microRNAs in vascular diseases.

Magenta A, Greco S, Gaetano C, Martelli F - Int J Mol Sci (2013)

Bottom Line: They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance.In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity.In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity.

View Article: PubMed Central - PubMed

Affiliation: Istituto Dermopatico del'Immacolata-IRCCS, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy. ale.magenta@gmail.com

ABSTRACT
Oxidative stress has been demonstrated to play a causal role in different vascular diseases, such as hypertension, diabetic vasculopathy, hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen species (ROS) production is known to impair endothelial and vascular smooth muscle cell functions, contributing to the development of cardiovascular diseases. MicroRNAs (miRNAs) are non-coding RNA molecules that modulate the stability and/or the translational efficiency of target messenger RNAs. They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance. In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity. In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity. In this review, we will discuss miRNAs modulated by ROS or involved in ROS production, and implicated in vascular diseases in which redox imbalance has a pathogenetic role.

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Related in: MedlinePlus

miR-210 and mitochondrial activity regulation. miR-210 inhibits mitochondrial oxidative phosphorylation inhibiting a series of targets: ISCU1 and ISCU2, participating in the assembly of iron sulfur (FeS)clusters, that, in turn, are present in several electron transport chain and TCA cycle components; COX10, a component of mitochondrial complex I and complex IV; FECH, which is the last enzyme in heme biosynthesis; SDHD, one of the subunits of the inner mitochondrial enzyme succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate during mitochondrial respiration. The inhibition of PHDs by succinate and by GPD1L, which feedback to HIF1A, is also shown.
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f3-ijms-14-17319: miR-210 and mitochondrial activity regulation. miR-210 inhibits mitochondrial oxidative phosphorylation inhibiting a series of targets: ISCU1 and ISCU2, participating in the assembly of iron sulfur (FeS)clusters, that, in turn, are present in several electron transport chain and TCA cycle components; COX10, a component of mitochondrial complex I and complex IV; FECH, which is the last enzyme in heme biosynthesis; SDHD, one of the subunits of the inner mitochondrial enzyme succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate during mitochondrial respiration. The inhibition of PHDs by succinate and by GPD1L, which feedback to HIF1A, is also shown.

Mentions: miR-210 is currently regarded as “master miRNA” of hypoxic response, because it was found upregulated by hypoxia in virtually all the cell types tested to date [34,35]. Recent data demonstrate that HIF1A can block both mitochondrial respiration and mitochondrial electron transport chain (ETC) activity, through transcription activation of miR-210 in many cell types [34,35]. miR-210 contributes to this metabolic shift by downregulating several steps of the mitochondrial metabolism, including the ETC complexes (Figure 3). In particular, miR-210 is responsible for the repression of ISCU1 and ISCU2 expression [84,85]. ISCU targeting is particularly important, since ISCU participates in the assembly of iron sulfur clusters, that are present in several ETC and TCA cycle components [37]. Indeed, loss of function of ISCU represses the mitochondrial function and disrupts iron homeostasis [39]. Interestingly, it has been shown that transferrin receptor 1 (TfR) is another relevant target of miR-210 in hypoxia [86]. This may be important for the accurate homeostasis of iron levels within the cell, since miR-210 regulates the assembly of iron-sulfur clusters in hypoxia by means of ISCU repression. In fact, excess iron is toxic since it generates free radicals [38]. Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin [87]. The physiopathological consequence of frataxin deficiency is a severe reduction of iron-sulfur cluster biosynthesis, mitochondrial iron overload coupled to cellular iron dysregulation and an increased sensitivity to oxidative stress [87].


Oxidative stress and microRNAs in vascular diseases.

Magenta A, Greco S, Gaetano C, Martelli F - Int J Mol Sci (2013)

miR-210 and mitochondrial activity regulation. miR-210 inhibits mitochondrial oxidative phosphorylation inhibiting a series of targets: ISCU1 and ISCU2, participating in the assembly of iron sulfur (FeS)clusters, that, in turn, are present in several electron transport chain and TCA cycle components; COX10, a component of mitochondrial complex I and complex IV; FECH, which is the last enzyme in heme biosynthesis; SDHD, one of the subunits of the inner mitochondrial enzyme succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate during mitochondrial respiration. The inhibition of PHDs by succinate and by GPD1L, which feedback to HIF1A, is also shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3794730&req=5

f3-ijms-14-17319: miR-210 and mitochondrial activity regulation. miR-210 inhibits mitochondrial oxidative phosphorylation inhibiting a series of targets: ISCU1 and ISCU2, participating in the assembly of iron sulfur (FeS)clusters, that, in turn, are present in several electron transport chain and TCA cycle components; COX10, a component of mitochondrial complex I and complex IV; FECH, which is the last enzyme in heme biosynthesis; SDHD, one of the subunits of the inner mitochondrial enzyme succinate dehydrogenase that catalyzes the oxidation of succinate to fumarate during mitochondrial respiration. The inhibition of PHDs by succinate and by GPD1L, which feedback to HIF1A, is also shown.
Mentions: miR-210 is currently regarded as “master miRNA” of hypoxic response, because it was found upregulated by hypoxia in virtually all the cell types tested to date [34,35]. Recent data demonstrate that HIF1A can block both mitochondrial respiration and mitochondrial electron transport chain (ETC) activity, through transcription activation of miR-210 in many cell types [34,35]. miR-210 contributes to this metabolic shift by downregulating several steps of the mitochondrial metabolism, including the ETC complexes (Figure 3). In particular, miR-210 is responsible for the repression of ISCU1 and ISCU2 expression [84,85]. ISCU targeting is particularly important, since ISCU participates in the assembly of iron sulfur clusters, that are present in several ETC and TCA cycle components [37]. Indeed, loss of function of ISCU represses the mitochondrial function and disrupts iron homeostasis [39]. Interestingly, it has been shown that transferrin receptor 1 (TfR) is another relevant target of miR-210 in hypoxia [86]. This may be important for the accurate homeostasis of iron levels within the cell, since miR-210 regulates the assembly of iron-sulfur clusters in hypoxia by means of ISCU repression. In fact, excess iron is toxic since it generates free radicals [38]. Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin [87]. The physiopathological consequence of frataxin deficiency is a severe reduction of iron-sulfur cluster biosynthesis, mitochondrial iron overload coupled to cellular iron dysregulation and an increased sensitivity to oxidative stress [87].

Bottom Line: They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance.In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity.In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity.

View Article: PubMed Central - PubMed

Affiliation: Istituto Dermopatico del'Immacolata-IRCCS, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy. ale.magenta@gmail.com

ABSTRACT
Oxidative stress has been demonstrated to play a causal role in different vascular diseases, such as hypertension, diabetic vasculopathy, hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen species (ROS) production is known to impair endothelial and vascular smooth muscle cell functions, contributing to the development of cardiovascular diseases. MicroRNAs (miRNAs) are non-coding RNA molecules that modulate the stability and/or the translational efficiency of target messenger RNAs. They have been shown to be modulated in most biological processes, including in cellular responses to redox imbalance. In particular, miR-200 family members play a crucial role in oxidative-stress dependent endothelial dysfunction, as well as in cardiovascular complications of diabetes and obesity. In addition, different miRNAs, such as miR-210, have been demonstrated to play a key role in mitochondrial metabolism, therefore modulating ROS production and sensitivity. In this review, we will discuss miRNAs modulated by ROS or involved in ROS production, and implicated in vascular diseases in which redox imbalance has a pathogenetic role.

Show MeSH
Related in: MedlinePlus