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söndag 20 november 2016

Alkoholi ja solusykli, fork head genes

https://www.ncbi.nlm.nih.gov/pubmed/27720397
https://www.ncbi.nlm.nih.gov/pubmed/22879847 

Alcohol, fork head
 7 vastausta hakuun

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Items: 7

1.
Westerhoff M, Tretiakova M, Hart J, Gwin K, Liu X, Zhou M, Yeh MM, Antic T.
Hum Pathol. 2014 May;45(5):1010-4. doi: 10.1016/j.humpath.2013.12.015.
FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy.
KEYWORDS:
FOXL2; Hepatobiliary cystadenoma; Mixed epithelial and stromal tumor of the kidney; Ovarian-type stroma; Pancreatic mucinous cystic neoplasm
2.
Shen L, Liu Z, Gong J, Zhang L, Wang L, Magdalou J, Chen L, Wang H.
Toxicol Appl Pharmacol. 2014 Jan 15;274(2):263-73. doi: 10.1016/j.taap.2013.11.009.

Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".
ACCα; ACTB; ADIPOR2; AMPKα; APOB; CORT; CPT1α; Catch-up growth; FASN; FOXO1; G6Pase; GAPDH; GC; GC–MS; GLUT2; GSK3β; Glucocorticoid–insulin-like growth factor-1 axis; HFD; HMG-CoA reductase; HMGCR; HNF4; HPRT1; IGF-1; IGF-1 receptor; IGF-1R; IGFBP3; INSR; IRS1; IRS2; IUGR; JAK2; Janus kinase 2; LEPR; MS; MTTP; NAFLD; ND; Non-alcoholic fatty liver disease; PEE; PPARα; Prenatal ethanol exposure; SREBP1c; TG; Two-programming hypothesis; acetyl-CoA carboxylase α; adenosine monophosphate activated protein kinase α; adiponectin receptor 2; apolipoprotein B; carnitine palmitoyltransferase 1α; corticosterone; fatty acid synthase; fork-head transcriptional factor O1; gas chromatography–mass spectrometry; glucocorticoid; glucose transporter 2; glucose-6-phosphatase; glyceraldehyde-phosphate dehydrogenase; glycogen synthase kinase 3β; hepatocyte nuclear factor 4; high-fat diet; hypoxanthine phosphoribosyltransferase 1; insulin receptor; insulin receptor substrate 1; insulin receptor substrate 2; insulin-like growth factor binding protein 3; insulin-like growth factor-1; intrauterine growth retardation; leptin receptor; mTORC2; mammalian target of rapamycin complex 2; metabolic syndrome; microsomal triglyceride transfer protein; non-alcoholic fatty liver disease; normal diet; peroxisome proliferator activated receptor α; prenatal ethanol exposure; sterol regulatory element binding protein-1c; triglyceride; β actin
3.
De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, Cinti S, Cuppini R.
Nutr Metab Cardiovasc Dis. 2013 Jun;23(6):582-90. doi: 10.1016/j.numecd.2012.01.013.
 Brown adipose tissue (BAT) plays a major role in body energy expenditure counteracting obesity and obesity-associated morbidities. BAT activity is sustained by the sympathetic nervous system (SNS). Since a massive activation of the SNS was described during physical activity, we investigated the effect of endurance running training on BAT of young rats to clarify the role of exercise training on the activity and recruitment state of brown cells.
Male, 10-week-old Sprague Dawley rats were trained on a motor treadmill (approximately 60% of VO2max), 5 days/week, both for 1 and 6 weeks. The effect of endurance training was valuated using morphological and molecular approaches. Running training affected on the morphology, sympathetic tone and vascularization of BAT, independently of the duration of the stimulus. Functionally, the weak increase in the thermogenesis (no difference in UCP-1), the increased expression of PGC-1α and the membrane localization of MCT-1 suggest a new function of BAT. Visceral fat increased the expression of the FOXC2, 48 h after last training session and some clusters of UCP-1 paucilocular and multilocular adipocytes appeared.
Exercise seemed a weakly effective stimulus for BAT thermogenesis, but surprisingly, without the supposed metabolically hypoactive effects. The observed browning of the visceral fat, by a supposed white-to-brown transdifferentiation phenomena suggested that exercise could be a new physiological stimulus to counteract obesity by an adrenergic-regulated brown recruitment of adipocytes.
4.
Grønning LM, Baillie GS, Cederberg A, Lynch MJ, Houslay MD, Enerbäck S, Taskén K.
FEBS Lett. 2006 Jul 24;580(17):4126-30.
 Overexpression of forkhead transcription factor FOXC2 in white adipose tissue (WAT) leads to a lean phenotype resistant to diet-induced obesity. This is due, in part, to enhanced catecholamine-induced cAMP-PKA signaling in FOXC2 transgenic mice. Here we show that rolipram treatment of adipocytes from FOXC2 transgenic mice did not increase isoproterenol-induced cAMP accumulation to the same extent as in wild type cells. Accordingly, phosphodiesterase-4 (PDE4) activity was reduced by 75% and PDE4A5 protein expression reduced by 30-50% in FOXC2 transgenic WAT compared to wild type. Thus, reduced PDE4 activity in adipocytes from FOXC2 transgenic mice contributes to amplified beta-AR induced cAMP responses observed in these cells.
PMID:
16828089
6.
Yeon JE, Califano S, Xu J, Wands JR, De La Monte SM.
Hepatology. 2003 Sep;38(3):703-14.
Chronic ethanol consumption can cause sustained hepatocellular injury and inhibit the subsequent regenerative response. These effects of ethanol may be mediated by impaired hepatocyte survival mechanisms. The present study examines the effects of ethanol on survival signaling in the intact liver. Adult Long Evans rats were maintained on ethanol-containing or isocaloric control liquid diets for 8 weeks, after which the livers were harvested to measure mRNA levels, protein expression, and kinase or phosphatase activity related to survival or proapoptosis mechanisms. Chronic ethanol exposure resulted in increased hepatocellular labeling for activated caspase 3 and nuclear DNA damage as demonstrated using the TUNEL assay. These effects of ethanol were associated with reduced levels of tyrosyl phosphorylated (PY) IRS-1 and PI3 kinase, Akt kinase, and Erk MAPK activities and increased levels of phosphatase tensin homologue deleted on chromosome 10 (PTEN) mRNA, protein, and phosphatase activity in liver tissue. In vitro experiments demonstrated that ethanol increases PTEN expression and function in hepatocytes. However, analysis of signaling cascade pertinent to PTEN function revealed increased levels of nuclear p53 and Fas receptor mRNA but without corresponding increases in GSK-3 activity or activated BAD. Although fork-head transcription factor levels were increased in ethanol-exposed livers, virtually all of the fork-head protein detected by Western blot analysis was localized within the cytosolic fraction. In conclusion, chronic ethanol exposure impairs survival mechanisms in the liver because of inhibition of signaling through PI3 kinase and Akt and increased levels of PTEN. However, uncoupling of the signaling cascade downstream of PTEN that mediates apoptosis may account for the relatively modest degrees of ongoing cell loss observed in livers of chronic ethanol-fed rats.
PMID:
12939597

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