High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

Hasson, Sidgi S.; Al-Balushi, Mohammed Saeed; Yahmadi, Muzna Hamed Al; Al-Busaidi, Juma Zaid; Said, Elias A.; Othman, Mohammed; Sallam, Talal A.; Idris, Mohammed; Al-Jabri, Ali A.

doi:10.12980/apjtb.4.201414b126

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…Modification of the carbohydrate content of recombinant ZAG in the presence of CoCl 2 provokes the notion that differences in ZAG glycosylation are co-regulated by oxygen-sensing factors and that these differences affect biological function in vivo. Diseases associated with a rise in ZAG levels, such as cancer, AIDS [37] and chronic heart and kidney disease [40,135,136], often manifest dyspnoea due to highly interdependent symptoms such as fatigue, physical impairment, pulmonary hypertension, lung infections and heart failure [137][138][139]. It would be interesting to observe whether overall oxygen saturation affects the glycosylation pattern of ZAG.…”

Section: Discussionmentioning

confidence: 99%

“…The positive correlation between increased ZAG expression and weight loss has also been observed in mice suffering from tumour-induced cachexia [28–30]. ZAG is also elevated in chronic diseases of the heart [31], the kidney [32,33] and the lung [34–36], as well as in AIDS (acquired immunodeficiency syndrome) [37,38], all of which are also associated with the development of cachexia. However, ZAG levels are also significantly reduced during the early phase of sepsis, but increase again during recovery [39].…”

Section: Introductionmentioning

confidence: 95%

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Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3

Romauch

2020

Open Biol.

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Zinc-α2-glycoprotein (ZAG) is a major plasma protein whose levels increase in chronic energy-demanding diseases and thus serves as an important clinical biomarker in the diagnosis and prognosis of the development of cachexia. Current knowledge suggests that ZAG mediates progressive weight loss through β-adrenergic signalling in adipocytes, resulting in the activation of lipolysis and fat mobilization. Here, through cross-linking experiments, amine oxidase copper-containing 3 (AOC3) is identified as a novel ZAG binding partner. AOC3—also known as vascular adhesion protein 1 (VAP-1) and semicarbazide sensitive amine oxidase (SSAO)—deaminates primary amines, thereby generating the corresponding aldehyde, H 2 O 2 and NH 3 . It is an ectoenzyme largely expressed by adipocytes and induced in endothelial cells during inflammation. Extravasation of immune cells depends on amine oxidase activity and AOC3-derived H 2 O 2 has an insulinogenic effect. The observations described here suggest that ZAG acts as an allosteric inhibitor of AOC3 and interferes with the associated pro-inflammatory and anti-lipolytic functions. Thus, inhibition of the deamination of lipolytic hormone octopamine by AOC3 represents a novel mechanism by which ZAG might stimulate lipolysis. Furthermore, experiments involving overexpression of recombinant ZAG reveal that its glycosylation is co-regulated by oxygen availability and that the pattern of glycosylation affects its inhibitory potential. The newly identified protein interaction between AOC3 and ZAG highlights a previously unknown functional relationship, which may be relevant to inflammation, energy metabolism and the development of cachexia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3

Romauch

2020

Open Biol.

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“…Modification of the carbohydrate content of recombinant ZAG in the presence of CoCl 2 provokes the notion that differences in ZAG glycosylation are co-regulated by oxygen-sensing factors and that these differences affect biological function in vivo . Diseases associated with a rise in ZAG levels, such as cancer, AIDS [37] and chronic heart and kidney disease [40,133,134], often manifest dyspnea due to highly interdependent symptoms such as fatigue, physical impairment, pulmonary hypertension, lung infections and heart failure [135–137]. It would be interesting to observe whether overall oxygen saturation affects the glycosylation pattern of ZAG.…”

Section: Discussionmentioning

confidence: 99%

“…The positive correlation between increased ZAG expression and weight loss has also been observed in mice suffering from tumor-induced cachexia [28–30]. ZAG is also elevated in chronic diseases of the heart [31], the kidney [32,33] and the lung [34–36], as well as in AIDS (acquired immunodeficiency syndrome) [37,38], all of which are also associated with the development of cachexia. However, ZAG levels are also significantly reduced during the early phase of sepsis, but increase again during recovery [39].…”

Section: Introductionmentioning

confidence: 96%

Zinc-α2-Glycoprotein Is An Inhibitor Of Amine Oxidase Copper-Containing 3

Romauch¹

2019

Preprint

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6Zinc-alpha2-glycoprotein (ZAG) is a major plasma protein whose levels increase in 7 chronic energy-demanding diseases and thus serves as an important clinical biomarker 8 in the diagnosis and prognosis of the development of cachexia. Current knowledge 9 suggests that ZAG mediates progressive weight loss through β-adrenergic signaling in 10 adipocytes, resulting in the activation of lipolysis and fat mobilization. Here, through 11 crosslinking experiments, amine oxidase copper-containing 3 (AOC3) is identified as a 12 novel ZAG binding partner. AOC3 -also known as vascular adhesion protein 1 (VAP-1) 13 and semicarbazide sensitive amine oxidase (SSAO) -deaminates primary amines, 14 thereby generating the corresponding aldehyde, H2O2 and HN3. It is an ectoenzyme 15 largely expressed by adipocytes and induced in endothelial cells during inflammation. H2O2 has an insulinogenic effect. The observations described here suggest that ZAG acts 18 as an allosteric inhibitor of AOC3 and interferes with the associated pro-inflammatory 19 and anti-lipolytic functions. Thus, inhibition of the deamination of lipolytic hormone 20 octopamine by AOC3 represents a novel mechanism by which ZAG might stimulate 21 lipolysis. Furthermore, experiments involving overexpression of recombinant ZAG 22 reveal that its glycosylation is co-regulated by oxygen availability and that the pattern of 23 glycosylation affects its inhibitory potential. The newly identified protein interaction 24 2 between AOC3 and ZAG highlights a previously unknown functional relationship, which 25 may be relevant to inflammation, energy metabolism and the development of cachexia. 26 27 93 provide much-needed insight into the mechanism of ZAG function and stimulate future work 94 in basic and clinical research on ZAG.95 96 5 2 Results 97 2.1 ZAG binds to ectoenzyme AOC3 98To attempt to identify ZAG interaction partners, purified recombinant ZAG and freshly 99 prepared adipocyte plasma membranes were co-incubated and any physical interactions 100 between them were stabilized by a photoactivatable crosslinker molecule (Fig. 11). Both 101 human and murine ZAG (without leader sequence) were produced in E. coli after cloning in 102 the expression plasmid pGEX-6P-2 and affinity purified by GST (glutathione-S-transferase)-103 tag. Both purified human and mouse proteins (GST-hZAG and GST-mZAG, respectively) and 104 GST-tag aloneserving as a controlwere labeled with the photoactivatable crosslinker 105

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