Accumulation of steroidogenic acute regulatory protein mRNA, and decrease in the secretory and proliferative activity of rat adrenocortical cells in the presence of proteasome inhibitors

Ziolkowska, Agnieska; Tortorella, Cinzia; Nussdorfer, Gastone G.; Ruciński, Marcin; Majchrzak, Mariola; Malendowicz, Ludwik K.

doi:10.3892/ijmm.17.5.865

Cited by 10 publications

(13 citation statements)

References 22 publications

(31 reference statements)

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“…This observation appears to accord well with the previously described inhibitory effect of proteasome inhibitors on steroid secretion from freshly dispersed and cultured rat adrenocortical cells (9). In light of this, we suggest that the steroidogenic pathway is more sensitive to proteasome inhibitors than that regulating proliferative activity of regenerating adrenocortical cells in the rat.…”

Section: Discussionsupporting

confidence: 79%

“…Moreover, experimental data suggested stabilization of regulatory proteins upon treatment with proteasome inhibitors (7). In keeping with this contention, findings showed that the treatment with proteasome inhibitors promotes StAR protein accumulation and StAR mRNA expression in cultured rat preovulatory granulosa and adrenocortical cells, respectively (8,9). However, these changes were coupled to a rise in progesterone output from granulosa cells, but to a lowering in corticosterone production from adrenocortical cells.…”

Section: Introductionmentioning

confidence: 48%

“…This is a rather unexpected finding because proteasome inhibitors have been found to induce accumulation of StAR protein in cultured steroid secreting cells and to inhibit their proliferative activity (9). Moreover, MG115 has been reported to cause a complete blockade of G1/S and metaphase transitions, as well as a delayed progression through S phase in various cell types cultured in vitro (34).…”

Section: Discussionmentioning

confidence: 82%

“…Of interest, a 24-h exposure to proteasome inhibitors was found to decrease the proliferation rate of cultured adrenocortical cells (9). In this connection, we remind that beacon, a ubiquitin-like protein (10)(11)(12) expressed in the rat adrenal cortex (13,14), has been found to inhibit the growth of cultured adrenocortical cells (15).…”

Section: Introductionmentioning

confidence: 99%

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Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Ruciński¹,

Tortorella²,

Ziółkowska³

et al. 2008

Int J Mol Med

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Abstract.Previous studies have shown that proteasome inhibitors promote the accumulation of steroidogenic acute regulatory protein (StAR) in cultured rat adrenocortical cells. Unexpectedly, this response was associated with a moderate lowering in the corticosterone secretion and proliferation rate of cultured cells. Hence, we studied the effects of proteasome inhibitors MG115 and MG132 on the secretion and proliferative activity of the regenerating adrenal cortex in rats 5 days after surgery. Animals were given two subcutaneous injections of 0.15 or 1.5 nmol/100 g of inhibitors 24 and 12 h before decapitation. Real-time PCR and Western blotting showed that StAR expression, both mRNA and protein, was markedly lower in regenerating adrenals than in the intact gland of sham-operated rats. Neither MG115 nor MG132 affected StAR expression in regenerating gland. Inhibitors induced a slight decrease in the plasma concentrations of aldosterone and corticosterone, but did not significantly alter metaphase index of the regenerating adrenal cortex. Our findings provide the first evidence that down-regulation of StAR occurs during the early stages of adrenal regeneration. Moreover, this suggests that the steroidogenic pathway is more sensitive to proteasome inhibitors than that regulating proliferative activity of regenerating adrenal cortex in the rat.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 48%

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Ruciński¹,

Tortorella²,

Ziółkowska³

et al. 2008

Int J Mol Med

Self Cite

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“…Proliferation rate of cultured adrenocortical cells was assayed by the EZ4U non-radioactive cell proliferation and cytotoxic assay of Biomedica (Vienna, Austria), as detailed earlier (40,50). Briefly, cultures were incubated for the last 5 h with EZ4U and formazan production, which is linearly related to the cell number, was assayed by measuring absorbance at 490 nm wavelength in a microplate autoreader EL13 (Bio-Tek Instruments, Winooski, VT).…”

Section: Rt-pcrmentioning

confidence: 99%

Effects of neuromedin-U on immature rat adrenocortical cells: In vitro and in vivo studies

Ziółkowska¹,

Macchi²,

Trejter³

et al. 2008

Int J Mol Med

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Abstract. Neuromedin U (NMU) is a brain-gut peptide, that in the peripheral organs and tissues acts via a G protein-coupled receptor, called NMUR1. Reverse transcription-polymerase chain reaction showed the expression of NMUR1 mRNA in either cortex and medulla or dispersed zona glomerulosa and zona fasciculata-reticularis cells of the immature rat adrenals. Accordingly, immunocytochemistry demonstrated the presence of NMUR1-like immunoreactivity in the cortex and medulla of immature adrenals. NMU8 administration to immature rats was found to raise aldosterone, but not corticosterone, plasma concentration, without altering adrenal growth. Conversely, the exposure to NMU8 markedly enhanced the proliferative activity of immature rat inner adrenocortical cells in primary in vitro culture, without significantly affecting their corticosterone secretion. Collectively, our findings suggest that adrenals of immature rats may be a target for circulating NMU. However, the physiological significance and relevance of the adrenal effects of NMU remain to be ascertained.

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The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in Female Reproduction

Nagyová

2018

IJMS

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Fertilization of the mammalian oocyte requires interactions between spermatozoa and expanded cumulus extracellular matrix (ECM) that surrounds the oocyte. This review focuses on key molecules that play an important role in the formation of the cumulus ECM, generated by the oocyte-cumulus complex. In particular, the specific inhibitors (AG1478, lapatinib, indomethacin and MG132) and progesterone receptor antagonist (RU486) exerting their effects through the remodeling of the ECM of the cumulus cells surrounding the oocyte have been described. After gonadotropin stimulus, cumulus cells expand and form hyaluronan (HA)-rich cumulus ECM. In pigs, the proper structure of the cumulus ECM depends on the interaction between HA and serum-derived proteins of the inter-alpha-trypsin inhibitor (IαI) protein family. We have demonstrated the synthesis of HA by cumulus cells, and the presence of the IαI, tumor necrosis factor-alpha-induced protein 6 and pentraxin 3 in expanding oocyte-cumulus complexes (OCC). We have evaluated the covalent linkage of heavy chains of IαI proteins to HA, as the principal component of the expanded HA-rich cumulus ECM, in porcine OCC cultured in medium with specific inhibitors: AG1478 and lapatinib (both inhibitors of epidermal growth factor receptor tyrosine kinase activity); MG132 (a specific proteasomal inhibitor), indomethacin (cyclooxygenase inhibitor); and progesterone receptor antagonist (RU486). We have found that both RU486 and indomethacin does not disrupt the formation of the covalent linkage between the heavy chains of IαI to HA in the expanded OCC. In contrast, the inhibitors AG1478 and lapatinib prevent gonadotropin-induced cumulus expansion. Finally, the formation of oocyte-cumulus ECM relying on the covalent transfer of heavy chains of IαI molecules to HA has been inhibited in the presence of MG132.

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Accumulation of steroidogenic acute regulatory protein mRNA, and decrease in the secretory and proliferative activity of rat adrenocortical cells in the presence of proteasome inhibitors

Cited by 10 publications

References 22 publications

Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Steroidogenic acute regulatory protein gene expression, steroid-hormone secretion and proliferative activity of adrenocortical cells in the presence of proteasome inhibitors: In vivo studies on the regenerating rat adrenal cortex

Effects of neuromedin-U on immature rat adrenocortical cells: In vitro and in vivo studies

The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in Female Reproduction

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