Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold

Horváth, Balázs; Spies, Claudia; Horváth, Gyöngyi; Kox, Wolfgang J.; Miyamoto, Suzanne; Barry, Sean J.; Warden, Craig H; Bechmann, Ingo; Diano, Sabrina; Heemskerk, Jill; Horváth, Tamas L.

doi:10.1016/s0006-2952(02)01167-x

Cited by 33 publications

(22 citation statements)

References 23 publications

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“…Ethanol sensitivity was decreased in UCP2-overexpressing mice and increased in UCP2 KO mice. UCP2 also modified the impairment of pain and temperature sensation induced by ethanol, which is consistent with localization of UCP2 in primary sensory afferents of the spinal cord (38). Overexpression of UCP1 or UCP3 is also neuroprotective in glucose-induced neuronal cell death through glucose-induced superoxide production and glucose-induced mitochondrial hyperpolarization (83).…”

Section: Uncoupling Proteins In the Nervous System 1177supporting

confidence: 78%

“…UCP2 mRNA is ubiquitously expressed in various tissues, including brain in rodents (38,72), and is mainly neuronal, although there is some debate about whether UCP2 protein is expressed predominantly in macrophages under basal conditions (73). UCP4 message is exclusively in brain (58), whereas BMCP1/ UCP5 is expressed in brain and several other tissues, including heart and kidney (45,48,74).…”

Section: Expression and Function Of Ucps In Brainmentioning

confidence: 99%

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Mitochondrial Uncoupling Proteins in the Central Nervous System

Kim-Han

Dugan

2005

Antioxidants & Redox Signaling

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Section: Uncoupling Proteins In the Nervous System 1177supporting

confidence: 78%

Section: Expression and Function Of Ucps In Brainmentioning

confidence: 99%

Mitochondrial Uncoupling Proteins in the Central Nervous System

Kim-Han

Dugan

2005

Antioxidants & Redox Signaling

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“…The mRNA is very widespread in most organs of the body and this has been one reason for ascribing to UCP2 a broad significance in metabolism. However, the development and verification of antibodies to UCP2 has been very slow, and only very few studies with antibodies verified by testing in UCP2-ablated mice exist (Pecqueur et al 2001;Zhang et al 2001;Horvath et al 2002;Krauss et al 2002). The outcome of these studies is that the antibodies used in most earlier studies recognised many proteins other than UCP2.…”

Section: The Novel Uncoupling Proteinsmentioning

confidence: 99%

The ‘Novel’‘Uncoupling’ Proteins UCP2 and UCP3: What Do They Really do? Pros and Cons for Suggested Functions

Nedergaard¹,

Cannon

2003

Experimental Physiology

207

150

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The scientifically novel, but evolutionarily ancient, so‐called uncoupling proteins 2 and 3 (UCP2, UCP3) are structually similar to the archetypical uncoupling protein UCP1. A series of suggestions have been forwarded for their physiological function. We discuss systematically here the pros and cons for these suggestions. We conclude that the novel UCPs do not seem to be physiologically relevant uncoupling proteins; the uncoupling property was apparently a late introduction into the subfamily through the evolution of UCP1. Physiological functions ascribed to UCP2 and UCP3 based on their purported uncoupling property may have to be revised (i.e. any type of thermogenesis, including protection against obesity, protection against the formation of reactive oxygen species and thermogenic involvement in the fever response). The presence of a mixed genetic background in most published studies of UCP2 or UCP3 gene‐ablated mice also means that data concerning marked differences in diabetes propensity, infection sensitivity and production of reactive oxygen species may require confirmation in backcrossed mice. The increased expression of UCP2 and UCP3 under conditions of increased fatty acid metabolism implies an as yet undefined role in lipid metabolism. Thus, the novel UCPs should probably be considered as mitochondrial carriers, and the challenge now is to identify the transported molecule.

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“…However, under pathologic conditions such as during inflammation (4) or steatosis, it increases (5); UCP2 gene expression has also been shown to occur in the hepatocytes of both normal adult rodents and healthy human adults, in the central area of the lobules (2). The role of UCP2 in obesity and liver disease is substantiated by the evidence that UCP2 enhanced fat accumulation in the liver, increased insulin resistance (6) and stimulated protective peripheral and central neural mechanisms in acute ethanol intake (7).…”

Section: Introductionmentioning

confidence: 99%

Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

Vimaleswaran

Cavadino

Verweij

et al. 2015

European Journal of Endocrinology

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Background and objective: Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (nZ20 242). Design and methods: The study populations included the Northern Finland Birth Cohort 1966 (nZ4996), Netherlands Study of Depression and Anxiety (nZ1883) and LifeLines Cohort Study (nZ13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test. Results: In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (P interaction Z0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations).

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Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold

Cited by 33 publications

References 23 publications

Mitochondrial Uncoupling Proteins in the Central Nervous System

Mitochondrial Uncoupling Proteins in the Central Nervous System

The ‘Novel’‘Uncoupling’ Proteins UCP2 and UCP3: What Do They Really do? Pros and Cons for Suggested Functions

Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

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