Increased uncoupling protein-2 gene expression in brain of lipopolysaccharide-injected mice: role of tumour necrosis factor-α?

Busquets, Sı́lvia; Álvarez, Belén; Royen, Martin E. van; Figueras, Maria Teresa; López‐Soriano, Francisco J.; Argilés, Josep Μ.

doi:10.1016/s0167-4889(00)00126-9

Cited by 25 publications

(15 citation statements)

References 43 publications

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“…This neuronal induction of UCP2 mRNA by KA was more extensive in 129T2SvEmsJ, a KAsensitive mouse strain, than in C57BL/6J, a KA-insensitive one, suggesting a specific link between UCP2 in KA excitotoxicity (17). Lipopolysaccharide, a commonly-used activator of oxidative stress, induced UCP2 mRNA, but not BMCP1/ UCP5 mRNA in mice (12). Administration of a ketogenic diet increased mitochondrial respiration by fatty acids, possibly through induction of one or more uncoupling proteins (80).…”

Section: Expression and Function Of Ucps In Brainmentioning

confidence: 87%

Mitochondrial Uncoupling Proteins in the Central Nervous System

Kim-Han

Dugan

2005

Antioxidants & Redox Signaling

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Section: Expression and Function Of Ucps In Brainmentioning

confidence: 87%

Mitochondrial Uncoupling Proteins in the Central Nervous System

Kim-Han

Dugan

2005

Antioxidants & Redox Signaling

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“…Patients with septic encephalopathy have a higher mortality rate compared with those without brain involvement, likely reflecting the severity of the disease and the direct adverse effects of brain involvement. The pathogenesis of septic encephalopathy is multifactorial and includes circulatory and metabolic derangements, 39 inflammation and infections 40 of the brain. …”

Section: Discussionmentioning

confidence: 99%

The role of the complement cascade in endotoxin-induced septic encephalopathy

Jacob

Hensley

Safratowich

et al. 2007

Laboratory Investigation

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The complement system normally eliminates bacteria and has a protective effect. However, in an inflammatory setting such as sepsis, an exaggerated or insufficient activation of this cascade can have deleterious effect through the activation of glial cells, secretion of proinflammatory cytokines and generation of other toxic products. The aim of the present study was to investigate the role of the complement cascade in septic encephalopathy, through the passive injection of endotoxin/lipopolysaccharide (LPS) into mice overexpressing the potent complement inhibitor, CR1-related y (Crry-tg). Increased gliosis occurred in brains of endotoxemic mice. Concomitant with this, there was a significant rise in mRNA expression of GFAP, CD45 and proinflammatory molecules, TLR4, TNF-a and NO, in these brains. Consistent with the capacity of these inflammatory mediators, there was increased apoptosis as determined by DNA fragmentation and TUNEL staining on LPS treatment, which occurred through the Akt pathway. In addition, there was increased water content in brain, similar to cerebral edema observed in sepsis. Relative to wild-type mice, complement-inhibited mice had an attenuated inflammatory response, decreased edema and reduced apoptosis. Therefore, we demonstrate for the first time that the complement cascade appears to be one of the key players that cause brain pathology in an endotoxemic setting and therefore is a viable therapeutic target.

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“…The development of fever includes a transient increase in heat production, and the novel uncoupling proteins could mediate this increase. Indeed, after injection of lipopolysaccharide (LPS), which induces fever, there is a very marked increase in the mRNA (or protein) level of UCP2 in a number of tissues, including lung (Pecqueur et al 2001), brain (Busquets et al 2001) and liver (Cortez-Pinto et al 1998;Faggioni et al 1998), and of UCP3 in skeletal muscle (Yu et al 2000a). …”

Section: Ucp2/ucp3 Are Thermogenically (Or Otherwise) Involved In Fevermentioning

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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Increased uncoupling protein-2 gene expression in brain of lipopolysaccharide-injected mice: role of tumour necrosis factor-α?

Cited by 25 publications

References 43 publications

Mitochondrial Uncoupling Proteins in the Central Nervous System

Mitochondrial Uncoupling Proteins in the Central Nervous System

The role of the complement cascade in endotoxin-induced septic encephalopathy

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

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