LC-MS/MS Quantification of Zn-α2 Glycoprotein: A Potential Serum Biomarker for Prostate Cancer

Bondar, Olga P.; Barnidge, David R.; Klee, Eric W.; Davis, Brian J.; Klee, George G.

doi:10.1373/clinchem.2006.079681

Cited by 117 publications

(82 citation statements)

References 18 publications

(17 reference statements)

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“…The Kd values are in the range expected, both from studies on the stimulation of lipolysis (10), and cyclic AMP production by ZAG. However, they are more than 10-times lower than the human plasma concentration reported using an ELISA (600nM), (25), but are comparable with that reported using mass spectrometry (85nM) (26). If the former value was true ZAG would be maximally stimulating the 2-and 3-AR at normal plasma concentrations, which is clearly not correct.…”

Section: Discussionmentioning

confidence: 63%

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Russell

Tisdale

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Objectives:The goal of the current study is to determine whether the -adrenoreceptor (-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-2-glycoprotein (ZAG). Material and Methods:This has been investigated in CHO-K1 cells transfected with the human 1-, 2-, 3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranonol.Results: ZAG bound to the 3-AR with higher affinity (Kd 46+1nM) than the 2-AR (Kd 71+3nM) while there was no binding to the 1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various -AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of 3-AR in gastrocnemius muscle, and in white and brown adipose tissue, but had no effect on expression of 1-and 2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, was completely attenuated by the non-specific -AR antagonist propranolol. Conclusion:The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a -3AR, or possibly a 2-AR.

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Section: Discussionmentioning

confidence: 63%

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Russell

Tisdale

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…2 The concentration of ZAG in normal human plasma or serum has been variously reported as between 3.65 and 140 mg ml À1 in different populations using various analytical techniques. [3][4][5] ZAG was initially reported to be correlated with body weight loss of cancer patients with cachexia, a severe life-threatening wasting syndrome defined by massive depletion of both adipose and skeletal muscle tissues in 1998. 6 The concentration of serum ZAG in cancer patients with cachexia was 20-fold higher than that of age and sex-matched normal people.…”

Section: Introductionmentioning

confidence: 99%

Zinc-α2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue

Zhang²,

et al. 2009

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Context: Zinc-a2-glycoprotein (ZAG) was found to influence lipolysis in adipose tissue and has recently been proposed as a candidate factor in the regulation of body weight. Objective: To elucidate the association of serum ZAG level with body weight and percentage of body fat in normal, obese subjects and high-fat diet (HFD)-induced obese mice. Design: The relationship between serum ZAG and obesity-related parameters was studied in 44 human subjects and 36 mice fed standard food and HFD. Furthermore, the effects of ZAG overexpression on adipose tissue of mice was also evaluated by using a liposome transfection method. Results: Serum ZAG level was significantly lower in obese patients and obese mice in comparison to that in people and mice with normal weight. The further statistical analysis demonstrated that ZAG level was negatively correlated with body weight (r ¼ À0.62, Po0.001), body mass index (r ¼ À0.64, Po0.001), waist circumference(r ¼ À0.68, Po0.001), hip circumference (r ¼ À0.60, Po0.001), percentage of body fat (r ¼ À0.52, P ¼ 0.03) and fat mass(r ¼ À0.59, P ¼ 0.01) in human subjects after adjustment for age and sex. Furthermore, ZAG overexpression in mice reduced body weight and the percentage of epididymal fat. The decreased FAS, ACC1 and DGAT mRNA and the increased HSL mRNA were also observed in epididymal adipose tissue in ZAG overexpression mice. Conclusion: ZAG is closely linked to obesity. Serum ZAG level is inversely associated with body weight and percentage of body fat. The action of ZAG is associated with downregulated lipogenic enzymes and upregulated lipolytic enzyme expressions in adipose tissue of mice.

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“…16 ZAG is overexpressed by several types of malignant tumors, such as cancers of breast, prostate, bladder and lung. [17][18][19][20] As serum ZAG levels are elevated in patients with prostate 18,21 and cervical 22 cancers, ZAG has been proposed to serve as a potential biomarker for these carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

et al. 2010

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The importance of white adipose tissue in the control of energy balance is now firmly recognized. In addition to fuel storage, adipocytes secrete an array of proteins factors (adipokines), which regulate multiple physiological and metabolic processes as well as influence body fat accumulation. Zinc-a2-glycoprotein (ZAG), a lipid mobilizing factor initially characterized as a tumor product associated with cachexia, has recently been identified as a novel adipokine. Although the exact role of ZAG in adipose tissue remains to be clarified, there is evidence that ZAG expression appears to be inversely related to adiposity, being upregulated in cachexia whereas reduced in obesity. Investigations on the regulation of ZAG give insights into its potential function in adipose tissue with a link to lipid mobilization and an anti-inflammatory action. Recent work shows that ZAG stimulates adiponectin secretion by human adipocytes. Data from genetic studies suggest that ZAG may be a candidate gene for body weight regulation; this is supported by the demonstration that ZAG-knockout mice are susceptible to weight gain, whereas transgenic mice overexpressing ZAG exhibit weight loss. The present review summarizes these new perspectives of ZAG and the potential mechanisms by which it might modulate adipose tissue mass and function.

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LC-MS/MS Quantification of Zn-α2 Glycoprotein: A Potential Serum Biomarker for Prostate Cancer

Cited by 117 publications

References 18 publications

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Zinc-α2-glycoprotein is involved in regulation of body weight through inhibition of lipogenic enzymes in adipose tissue

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

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