Differential modulation of expression of the two acylphosphatase isoenzymes by thyroid hormone

Abstract

The modulation of expression of the skeletal muscle and erythrocyte acylphosphatase isoenzymes by thyroid hormone has been investigated. Our results indicate a differential regulation of the two enzymic isoforms by tri-iodothyronine (T3) in K562 cells in culture: an increase in the specific mRNA during T3-stimulation is shown only for the skeletal muscle isoenzyme. A fast and transient T3 induction of the accumulation of the specific mRNA can be observed, reaching a maximum 8 h after hormone treatment and then rapidly decreasing almost to the steady-state level after 24 h. A nuclear run-on assay was performed to explore the mechanisms of this regulation. These studies indicate that T3 induction of skeletal muscle acylphosphatase mRNA is due, at least in part, to a fast and transient increase in the rate of gene transcription, within 4 h after hormone administration. A very rapid decrease is then observed within a further 2 h. T3-dependent accumulation of the mRNA for the skeletal muscle acylphosphatase requires ongoing protein synthesis, as confirmed by inhibition with cycloheximide or puromycin. These findings indicate that the transcriptional regulation of the gene may be indirect.

Acylphosphatase possesses nucleoside triphosphatase and nucleoside diphosphatase activities

“…Previous studies have demonstrated that overexpression of acylphosphatase is accompanied by cell differentiation [33][34][35], and that the enzyme migrates into the nucleus during differentiation [36] as well as during apoptosis [37]. Our previous findings on the role of acylphosphatase in cell differentiation have indicated that : (i) the level of the acylphosphatase MT isoenzyme increases about 10-fold during myotube differentiation of cultured myoblasts, along with an increase in the levels of musclespecific proteins [33] ; (ii) the ectopic expression of the MT isoenzyme in K562 cells accelerates their erythrocyte differentiation [34] ; (iii) tri-iodothyronine (T $ ), a bland differentiating agent for K562 cells, activates the MT acylphosphatase gene, so that enzyme concentration is enhanced after hormone treatment. In contrast, T $ has no effect on the CT isoform, indicating that the two genes are differently regulated [34].…”

Acylphosphatase overexpression triggers SH-SY5Y differentiation towards neuronal phenotype

“…These observations, taken together, indicate that the two AcP isoenzymes are subject to different regulatory mechanisms during differentiation. As an example, thyroid hormone treatment induces the MT isoform but exerts no influence upon the CT isoform in K562 cells [15]. Translation of MT AcPase mRNA is regulated by the presence of an additional upstream AUG codon and a very stable stem-loop structure in the 5¢ untranslated (UTR) region, which provides stringent control of AcPase expression.…”

Hydrogen Peroxide Triggers the Formation of a Disulfide Dimer of Muscle Acylphosphatase and Modifies Some Functional Properties of the Enzyme

“…3, 4, and citations therein), because it displays hydrolytic activity against the aspartyl-phosphate intermediates formed during the action of Na ϩ ,K ϩ -and Ca 2ϩ -ATPases. Other reports involve ACP in cell differentiation and apoptosis (5)(6)(7); this is because the enzyme is overexpressed when cells are induced to differentiate by certain agents, and it is able to migrate into the nucleus during both differentiation and apoptosis (8,9). The primary structure of the two isoenzymes differs in about 50% of amino acid positions, but they display very similar folds: Both consist of a five-stranded antiparallel twisted ␤-sheet flanked on one side by two antiparallel ␣-helices running parallel to the ␤-sheet (10).…”