Mitochondrial Uncoupling Proteins in the Central Nervous System

Kim-Han, Jeong Sook; Dugan, Laura L.

doi:10.1089/ars.2005.7.1173

Cited by 87 publications

(63 citation statements)

References 86 publications

(92 reference statements)

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“…UCPs limit free radical production, 15,22,23 whereas SIRT3 is a mitochondrial acetyl transferase known to decrease ROS through a number of pathways. 24 Pretreatment with CC prevented I/R-induced increase in UCP2 and SIRT3 ( Figure 5, B and C), consistent with AMPK-mediated regulation of UCP2 and SIRT3.…”

Section: Inhibition Of Ampk Exacerbates I/r Kidney Injurymentioning

confidence: 99%

“…I/R in WT kidneys increases AMPK activity and the expression of STC1, UCP2, and silent mating type information regulation 2 homolog 3 (SIRT3; also known as sirtuin 3). UCPs limit free radical production, 22,23 whereas SIRT3, a mitochondrial acetyltransferase, decreases ROS through a number of pathways, 24 but its functions in the kidney are largely unknown. Pretreatment of WT mice with 6-[4-(2-piperidin-1-ylethoxy) phenyl]-3-pyridin-4-ylpyrazolo [1,5-a] pyrimidine (compound C [CC]), a pharmacologic inhibitor of AMPK, 25,26 abolishes I/R-induced AMPK activation, diminishes the expression of SIRT3 and UCP2, and is associated with increased ROS production and worse morphologic changes.…”

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confidence: 99%

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Stanniocalcin-1 Inhibits Renal Ischemia/Reperfusion Injury via an AMP-Activated Protein Kinase-Dependent Pathway

Pan¹,

Huang²,

Belousova³

et al. 2015

Journal of the American Society of Nephrology

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AKI is associated with increased morbidity, mortality, and cost of care, and therapeutic options remain limited. Reactive oxygen species are critical for the genesis of ischemic AKI. Stanniocalcin-1 (STC1) suppresses superoxide generation through induction of uncoupling proteins (UCPs), and transgenic overexpression of STC1 inhibits reactive oxygen species and protects from ischemia/reperfusion (I/R) kidney injury. Our observations revealed high AMP-activated protein kinase (AMPK) activity in STC1 transgenic kidneys relative to wild-type (WT) kidneys; thus, we hypothesized that STC1 protects from I/R kidney injury through activation of AMPK. Baseline activity of AMPK in the kidney correlated with the expression of STCs, such that the highest activity was observed in STC1 transgenic mice followed (in decreasing order) by WT, STC1 knockout, and STC1/STC2 double-knockout mice. I/R in WT kidneys increased AMPK activity and the expression of STC1, UCP2, and sirtuin 3. Inhibition of AMPK by administration of compound C before I/R abolished the activation of AMPK, diminished the expression of UCP2 and sirtuin 3, and aggravated kidney injury but did not affect STC1 expression. Treatment of cultured HEK cells with recombinant STC1 activated AMPK and increased the expression of UCP2 and sirtuin 3, and concomitant treatment with compound C abolished these responses. STC1 knockout mice displayed high susceptibility to I/R, whereas pretreatment of STC1 transgenic mice with compound C restored the susceptibility to I/R kidney injury. These data suggest that STC1 is important for activation of AMPK in the kidney, which mediates STC1-induced expression of UCP2 and sirtuin 3 and protection from I/R.

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Section: Inhibition Of Ampk Exacerbates I/r Kidney Injurymentioning

confidence: 99%

mentioning

confidence: 99%

Stanniocalcin-1 Inhibits Renal Ischemia/Reperfusion Injury via an AMP-Activated Protein Kinase-Dependent Pathway

Pan¹,

Huang²,

Belousova³

et al. 2015

Journal of the American Society of Nephrology

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“…Proton leak is known to significantly contribute to the control of respiration in mitochondria in state 4 and to some extent in state 3. Therefore, uncoupling proteins also play an important role in sustaining proton leak, preventing excessive H + gradient, and, subsequently, avoiding excessive ROS production (88,109).…”

Section: Fig 5 Ros-dependent Regulation Of Cellular Ca 21 Handing Amentioning

confidence: 99%

Mitochondrial Ion Channels/Transporters as Sensors and Regulators of Cellular Redox Signaling

O‐Uchi

Ryu

Jhun

et al. 2014

Antioxidants & Redox Signaling

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Significance: Mitochondrial ion channels/transporters and the electron transport chain (ETC) serve as key sensors and regulators for cellular redox signaling, the production of reactive oxygen species (ROS) and nitrogen species (RNS) in mitochondria, and balancing cell survival and death. Although the functional and pharmacological characteristics of mitochondrial ion transport mechanisms have been extensively studied for several decades, the majority of the molecular identities that are responsible for these channels/transporters have remained a mystery until very recently. Recent Advances: Recent breakthrough studies uncovered the molecular identities of the diverse array of major mitochondrial ion channels/transporters, including the mitochondrial Ca 2+ uniporter pore, mitochondrial permeability transition pore, and mitochondrial ATP-sensitive K + channel. This new information enables us to form detailed molecular and functional characterizations of mitochondrial ion channels/transporters and their roles in mitochondrial redox signaling. Critical Issues: Redox-mediated post-translational modifications of mitochondrial ion channels/transporters and ETC serve as key mechanisms for the spatiotemporal control of mitochondrial ROS/RNS generation. Future Directions: Identification of detailed molecular mechanisms for redox-mediated regulation of mitochondrial ion channels will enable us to find novel therapeutic targets for many diseases that are associated with cellular redox signaling and mitochondrial ion channels/transporters. Antioxid. Redox Signal. 21, 987-1006.

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“…Moreover, mammalian UCP2 (ubiquitously expressed in almost all mammalian tissues) and UCP3 (predominantly expressed in skeletal muscle) might be implicated in numerous physiological and pathological phenomena, e.g., body weight regulation, fatty acid metabolism, inflammation, diabetes, and heart failure (Nedergaard et al 2005;Harper and Gerritis 2004). The brain specific UCPs, UCP4 and UCP5, might play an important role in apoptosis, neuroprotection, neuronal differentiation and synaptic plasticity in the brain (Kim-Han and Dugan 2005).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

Słocińska

Antos-Krzemińska

Rosiński

et al. 2011

J Bioenerg Biomembr

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We have identified and characterized an uncoupling protein in mitochondria isolated from leg muscle and from fat body, an insect analogue tissue of mammalian liver and adipose tissue, of the cockroach Gromphadorhina coquereliana (GcUCP). This is the first functional characterization of UCP activity in isolated insect mitochondria. Bioenergetic studies clearly indicate UCP function in both insect tissues. In resting (non-phosphorylating) mitochondria, cockroach GcUCP activity was stimulated by the addition of micromolar concentrations of palmitic acid and inhibited by the purine nucleotide GTP. Moreover, in phosphorylating mitochondria, GcUCP activity was able to divert energy from oxidative phosphorylation. Functional studies indicate a higher activity of GcUCP-mediated uncoupling in cockroach muscle mitochondria compared to fat body mitochondria. GcUCP activation by palmitic acid resulted in a decrease in superoxide anion production, suggesting that protection against mitochondrial oxidative stress may be a physiological role of UCPs in insects. GcUCP protein was immunodetected using antibodies raised against human UCP4 as a single band of around 36 kDa. GcUCP protein expression in cockroach muscle mitochondria was significantly higher compared to mitochondria isolated from fat body. LC-MS/MS analyses revealed 100% sequence identities for peptides obtained from GcUCP to UCP4 isoforms from D. melanogaster (the highest homology), human, rat or other insect mitochondria. Therefore, it can be proposed that cockroach GcUCP corresponds to the UCP4 isoforms of other animals.

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Mitochondrial Uncoupling Proteins in the Central Nervous System

Cited by 87 publications

References 86 publications

Stanniocalcin-1 Inhibits Renal Ischemia/Reperfusion Injury via an AMP-Activated Protein Kinase-Dependent Pathway

Stanniocalcin-1 Inhibits Renal Ischemia/Reperfusion Injury via an AMP-Activated Protein Kinase-Dependent Pathway

Mitochondrial Ion Channels/Transporters as Sensors and Regulators of Cellular Redox Signaling

Identification and characterization of uncoupling protein 4 in fat body and muscle mitochondria from the cockroach Gromphadorhina cocquereliana

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