Immunohistochemical analysis of human skeletal muscle AMP deaminase deficiency. Evidence of a correlation between the muscle HPRG content and the level of the residual AMP deaminase activity

Sabbatini, Antonietta Raffaella Maria; Toscano, Antonio; Aguennouz, M.; Martini, Daniela; Polizzi, Enza; Ranieri-Raggi, Maria; Moir, Arthur J. G.; Migliorato, Alba; Musumeci, Olimpia; Vita, Giuseppe; Raggi, Antonio

doi:10.1007/s10974-006-9059-4

Cited by 10 publications

(20 citation statements)

References 38 publications

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“…An anti HPRG antibody selectively marked the type IIB fibers that contain the highest level of AMPD isoform M [54]. Furthermore, the immunological reaction of the anti-HPRG antibody and of an antibody anti-AMPD (isoform M) in human skeletal muscle biopsies from patients with AMPD deficiency clearly indicated a correlation between the muscle content of the HPRG-like protein and the level of AMPD activity [55]. Taken together, these data suggest that HPRG, functioning as an intracellular zinc chaperone, may be involved in the assembly and maintenance of skeletal muscle AMPD.…”

Section: The Histidine-proline-rich Central Region Of Hprg: Potentialmentioning

confidence: 94%

Structure-function relationships in mammalian histidine-proline-rich glycoprotein

Ronca

Raggi

2015

Biochimie

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Section: The Histidine-proline-rich Central Region Of Hprg: Potentialmentioning

confidence: 94%

Structure-function relationships in mammalian histidine-proline-rich glycoprotein

Ronca

Raggi

2015

Biochimie

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“…In healthy human skeletal muscle, an anti-HPRG antibody selectively bound to type IIB fibers that are well known to contain the highest level of AMPD activity, suggesting an association of the HPRG-like protein to the enzyme isoform M [8]. An immunohistochemical study performed on human skeletal muscle biopsies from patients with AMPD deficiency and carried out utilising both the anti-HPRG antibody and an anti-AMPD antibody specific for the isoform M demonstrated a correlation between the muscle content of the HPRG-like protein and the level of AMPD activity [11]. …”

Section: Localization Site Of Biosynthesis and Primary Structure mentioning

confidence: 99%

“…This observation strongly suggests the presence of intracellular Zn-chaperones acting to make free zinc available for partner proteins could be critical for the physiological functions of Zn 2+ metalloenzymes. This is particularly true for skeletal muscle taking into account the results of the recent studies on the novel protein-protein complex formed by the Zn 2+ metalloenzyme AMP deaminase (AMPD, EC 3.5.4.6) and the zinc binding protein histidine-proline-rich glycoprotein (HPRG) [7,8,9,10,11]. …”

Section: Introductionmentioning

confidence: 99%

The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase

2014

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Metallochaperones function as intracellular shuttles for metal ions. At present, no evidence for the existence of any eukaryotic zinc-chaperone has been provided although metallochaperones could be critical for the physiological functions of Zn2+ metalloenzymes. We propose that the complex formed in skeletal muscle by the Zn2+ metalloenzyme AMP deaminase (AMPD) and the metal binding protein histidine-proline-rich glycoprotein (HPRG) acts in this manner. HPRG is a major plasma protein. Recent investigations have reported that skeletal muscle cells do not synthesize HPRG but instead actively internalize plasma HPRG. X-ray absorption spectroscopy (XAS) performed on fresh preparations of rabbit skeletal muscle AMPD provided evidence for a dinuclear zinc site in the enzyme compatible with a (μ-aqua)(μ-carboxylato)dizinc(II) core with two histidine residues at each metal site. XAS on HPRG isolated from the AMPD complex showed that zinc is bound to the protein in a dinuclear cluster where each Zn2+ ion is coordinated by three histidine and one heavier ligand, likely sulfur from cysteine. We describe the existence in mammalian HPRG of a specific zinc binding site distinct from the His-Pro-rich region. The participation of HPRG in the assembly and maintenance of skeletal muscle AMPD by acting as a zinc chaperone is also demonstrated.

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“…Moreover, in a recent immunohistochemical analysis, performed on human skeletal muscle biopsies of patients affected by AMPD deficiency, we have shown a positive correlation between the HRG muscle content and the total determined AMPD activity. 10 We previously suggested a new model for skeletal muscle AMPD, a 1:1 molecular adduct in which two AMPD catalytic subunits assemble with two HRG subunits. 11 However, the present data do not establish whether HRG permanently contributes to the structure of the enzyme or whether it simply binds the enzyme.…”

Section: Introductionmentioning

confidence: 99%

Evidence that muscle cells do not express the histidine-rich glycoprotein associated with AMP deaminase but can internalise the plasma protein

et al. 2011

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Histidine-rich glycoprotein (HRG) is synthesized by liver and is present at relatively high concentration in the plasma of vertebrates. We have previously described the association of a HRG-like molecule to purified rabbit skeletal muscle AMP deaminase (AMPD). We also provided the first evidence for the presence of a HRG-like protein in human skeletal muscle where a positive correlation between HRG content and total determined AMPD activity has been shown. In the present paper we investigate the origin of skeletal muscle HRG. The screening of a human skeletal muscle cDNA expression library using an anti-HRG antibody failed to reveal any positive clone. The RT-PCR analysis, performed on human skeletal muscle RNA as well as on RNA from the rhabdomyosarcoma (RD) cell line, failed to show any mRNA specific for the plasma HRG or for the putative muscle variant. When the RD cells were incubated with human plasma HRG, a time-dependent increase of the HRG immunoreactivity was detected both at the plasma membrane level and intracellularly. The internalisation of HRG was inhibited by the addition of heparin. The above data strongly suggest that skeletal muscle cells do not synthesize the muscle variant of HRG but instead can actively internalise it from plasma.

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Immunohistochemical analysis of human skeletal muscle AMP deaminase deficiency. Evidence of a correlation between the muscle HPRG content and the level of the residual AMP deaminase activity

Cited by 10 publications

References 38 publications

Structure-function relationships in mammalian histidine-proline-rich glycoprotein

Structure-function relationships in mammalian histidine-proline-rich glycoprotein

The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase

Evidence that muscle cells do not express the histidine-rich glycoprotein associated with AMP deaminase but can internalise the plasma protein

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