The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved insulin sensitivity by DHEA in muscle and liver of rats in vivo

Campbell, Carmen Sílvia Grubert; Caperuto, Luciana C.; Hirata, Aparecida Emiko; Araujo, Eliana P.; Velloso, Lı́cio A.; Saad, Mário J.A.; Carvalho, Carla Roberta de Oliveira

doi:10.1016/j.lfs.2004.06.017

Cited by 45 publications

(47 citation statements)

References 43 publications

(45 reference statements)

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“…Thus, the atypical PKC is uncoupled from the PI3K pathway in ovarian cancer cells and is more likely to be a PP2A target. This is in contrast to the situation in the majority of normal and malignant tissues, in which PKCζ functions as an insulin-dependent PI3K effector (39)(40)(41)(42)(43)(44). Importantly, overexpression of wildtype HRSL3, but not of its interaction-deficient mutant, also led to PKC phosphorylation, suggesting a direct link between the ability of HRSL3 to inhibit PP2A and to activate PKCζ.…”

Section: Resultsmentioning

confidence: 57%

Atypical Protein Kinase C ζ Exhibits a Proapoptotic Function in Ovarian Cancer

Nazarenko

Jenny

Keil

et al. 2010

Molecular Cancer Research

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Intracellular signaling governed by serine/threonine kinases comprises the molecular interface between cell surface receptors and the nuclear transcriptional machinery. The protein kinase C (PKC) family members are involved in the control of many signaling processes directing cell proliferation, motility, and survival. Here, we examined a role of different PKC isoenzymes in protein phosphatase 2A (PP2A) and HRSL3 tumor suppressordependent cell death induction in the ovarian carcinoma cell line OVCAR-3. Phosphorylation and activity of PKC isoenzymes were measured in response to PP2A or phosphoinositide 3-kinase inhibition or HRSL3 overexpression. These experiments indicated a regulation of PKCθ, ε, ζ, and ι through PP2A and/or HRSL3, but not of PKCα and β. Using isoform-specific peptide inhibitors and overexpression approaches, we verified a contribution to PP2A-and HRLS3-dependent apoptosis only for PKCζ, suggesting a proapoptotic function of this kinase. We observed a significant proportion of human ovarian carcinomas expressing high levels of PKCζ, which correlated with poor prognosis. Primary ovarian carcinoma cells isolated from patients also responded to okadaic acid treatment with increased phosphorylation of PKCζ and apoptosis induction. Thus, our data indicate a contribution of PKCζ in survival control in ovarian carcinoma cells and suggest that upregulation or activation of tyrosine kinase receptors in this tumor might impinge onto apoptosis control through the negative regulation of the atypical PKCζ. Mol Cancer Res; 8(6); 919-34. ©2010 AACR.

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Section: Resultsmentioning

confidence: 57%

Atypical Protein Kinase C ζ Exhibits a Proapoptotic Function in Ovarian Cancer

Nazarenko

Jenny

Keil

et al. 2010

Molecular Cancer Research

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“…Because of its accessibility, the gastrocnemius muscle has been previously studied to analyse the specific effects of DHEA on skeletal muscle (Hansen et al 1997;Aragno et al 2004;Campbell et al 2004). In the present study, a larger gastrocnemius size relative to total body mass was found in DHEA-treated rats compared with control ones.…”

Section: Discussionmentioning

confidence: 47%

Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats

et al. 2007

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The main objective of the present study was to examine the effects of dehydroepiandrosterone (DHEA) on the digestive efficiency of dietary protein and fat. Second, we analysed the specific changes in muscle composition induced by the hormone. DHEA was given in the diet (0·5 %, w/w) to 75-week-old, high-fat-fed Sprague -Dawley rats (n 11) for 13 weeks; age-and weight-matched rats fed on the same diet without DHEA supplementation were used as controls (n 10). To determine dietary protein and fat apparent digestibility coefficients, 1-week 24 h faecal depositions were collected. In parallel, urine N was assessed. These assays were performed twice, in the short term (2-week treatment) and in the long term (13-week treatment). Body and gastrocnemius muscle compositions were also analysed. The present results show that DHEA decreased energy intake, body weight, body fat, adipocyte size and number (P,0·001). The feed efficiency ratio indicates that DHEA-treated rats were less efficient in transforming nutrients fed into their own biomass. Also, a short-term reduction in protein digestibility (P, 0·05) and in body-protein degradation (P, 0·01) was found in DHEA-treated rats, resulting in an increased content of body protein (P,0·05). Gastrocnemius muscles were smaller, as a result of fat (P, 0·05) but not protein reduction. In conclusion, we confirm the slimming effect of DHEA and, for the first time, we demonstrate that DHEA has an effect at the digestive level. The anti-obesity properties of DHEA could be related to a reduction in protein digestibility in the short term and a protective effect on body protein with a selective mass loss from body fat.Dehydroepiandrosterone: Digestibility: Body protein: Gastrocnemius muscle: Obesity: High-fat diets Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are the most abundant circulating steroids in man and the precursors for most steroid hormones (Orentreich et al. 1984). Serum concentrations of DHEA and DHEA-S are age dependent; in man, they rapidly increase at puberty, reach their peak levels between 20 and 30 years of age, and then decrease gradually (Yamaji & Ibayashi, 1969;Orentreich et al. 1984;Vermeulen, 1995;Macario et al. 1999). This evolution, coincident with the incipient loss of physical performance, has led these hormones to be known as 'the hormones of youth ' (Nawata et al. 2002).Far from being just biochemical intermediates, these steroids per se have been reported to have positive effects in the prevention and treatment of certain pathologies, especially the age-related ones, such as cancer (Schwartz et al. 1988;Ratko et al. 1991;Kawai et al. 1995), CVD (Ebeling & Koivisto, 1994), cognitive deterioration (Yanase et al. 1996), insulin resistance and obesity (Williams et al. 1993).In man, the action of DHEA on obesity is not generally agreed. Some studies report no relationship between plasma levels of these steroids and body weight and fat (Azziz et al. 1991;Phillips, 1993;Barret-Connor & Ferrara, 1996;Macario et al. 1999), while others find a negative co...

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“…Outro efeito benéfico do DHEA observado é a redução da resistência à insulina que aparece com o envelhecimento (Han et al, 1998) e melhora da sinalização da insulina em tecido muscular e hepático (Campbell et al, 2004). Ainda em ratos envelhecidos, a administração de dose única de DHEA aumenta a secreção de insulina estimulada por glicose em ilhotas pancreáticas isoladas (Medina et al, 2006).…”

Section: Deidroepiandrosterona (Dhea)unclassified

“…Em estudos experimentais com animais, o tratamento com DHEA apresentou diversos efeitos benéficos, como redução da fibrose no miocárdio em ratos diabéticos (Aragno et al, 2008), retardo na formação de placas ateroscleróticas em coelhos (Hayashi et al, 2000), redução do ganho de peso corporal e depósito de gordura (Han et al, 1998), aumento da sensibilidade à insulina (Campbell et al, 2004) e secreção de insulina em ilhotas pancreáticas isoladas de ratos velhos (Medina et al, 2006) e redução da pressão arterial em ratas ovariectomizadas (Bhuiyan e Fukunaga, 2010). Além disso, em estudos in vitro, DHEA aumenta a proliferação endotelial (Williams et al, 2004) e protege células endoteliais contra apoptose , sendo que tais efeitos são independentes da ativação do receptor para estrogênio.…”

Section: Estudo Da Função Vascularunclassified

“…Em estudos experimentais foram descritos efeitos anti-diabetogênicos em camundongos ob/ob (Coleman et al, 1982), melhora da resistência períferica à insulina em ratos Wistar (Campbell et al, 2004 ;Mukasa et al, 1998) Existem diversas hipóteses que buscam explicar o desenvolvimento da resistência à insulina associado a obesisdade, situação observada na falta de estrogênios. Aumento das citocinas plasmaticas e teciduais devido a inflamação e aumento dos adipócitos pode levar a resistência à insulina, já que algumas citocinas como o fator de necrose tumoral alfa (TNFα) e a resistina são potentes inibidores da sinalização da insulina (Camporez et al, 2011;Jazet et al, 2003 as quais inibem a ação da insulina no fígado e músculo .…”

Section: Estudo Da Resistência Periférica à Insulinaunclassified

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Efeitos do deidroepiandrosterona (DHEA) sobre a função vascular e a resistência periférica à insulina em um modelo experimental de menopausa.

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The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved insulin sensitivity by DHEA in muscle and liver of rats in vivo

Cited by 45 publications

References 43 publications

Atypical Protein Kinase C ζ Exhibits a Proapoptotic Function in Ovarian Cancer

Atypical Protein Kinase C ζ Exhibits a Proapoptotic Function in Ovarian Cancer

Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats

Efeitos do deidroepiandrosterona (DHEA) sobre a função vascular e a resistência periférica à insulina em um modelo experimental de menopausa.

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