Pharmacologic and Biochemical Considerations of Dimethyl Sulfoxide

Wood, Don C.; Wood, Julianne

doi:10.1111/j.1749-6632.1975.tb25339.x

Cited by 132 publications

(55 citation statements)

References 62 publications

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“…DMSO, the widely used solvent in studies with proteasome inhibitors, is known to affect the function of several biological systems (16,17). Accordingly, our findings indicate that 0.3% DMSO enhances steroid secretion from either dispersed or cultured rat adrenocortical cells, although lowering StAR mRNA content after 24 h exposure.…”

Section: Discussionmentioning

confidence: 99%

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

Ziolkowska¹,

Tortorella²,

Nussdorfer³

et al. 2006

Int J Mol Med

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Abstract. Sporadic findings indicate that proteolysis may affect steroid secretion in rat ovary granulosa cells. We examined the effects of the proteasome inhibitors MG115 and MG101 on the in vitro secretion and growth of rat adrenocortical cells. MG115 and/or MG101 decreased within 120 min the aldosterone and corticosterone secretion from freshly dispersed zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells. After a 24-h incubation MG115 alone or with MG101 lowered corticosterone production and enhanced proliferation rate of cultured ZF/R cells, while MG101 was per se ineffective. Real-time polymerase chain reaction demonstrated that MG101 decreased steroidogenic acute regulatory protein (StAR) mRNA in cultured cells. MG115 was per se ineffective, but when added together with MG101 evoked a marked rise in StAR mRNA content. In light of the present findings, we conclude that i) protein breackdown by proteasomes is required for the maintenance of a normal secretory and proliferative activity of freshly dispersed or cultured rat adrenocortical cells; and ii) in long-term experiments, great caution must be taken in correlating StAR mRNA content and steroidogenic capacity. IntroductionIt is currently accepted that steroidogenic acute regulatory protein (StAR) plays a pivotal role in steroidogenesis, inasmuch as it regulates the rate-limiting step of this process (i.e. the translocation of cholesterol from the outer to the inner mitochondrial membrane) (reviewed in ref. 1). In steroidogenic cells the 37 kDa StAR preprotein is rapidly cleaved to the mature 30 kDa protein (2,3), and the estimated half-life of StAR preprotein trapped in the cytosol does not exceed 15 min (3,4). Hence, StAR preprotein must be produced continuously if steroidogenesis is to be maintained.Compelling evidence indicates that in most cultured mammalian cells under optimal nutritional conditions, 80-90% of the protein breakdown occurs via the proteasome pathway and only 10-20% via the lysosomal system (reviewed in ref. 5). Convincing findings show that the bulk of short-lived regulatory proteins, including StAR, is degraded by the ubiquitin-proteasome system (3,6), and there is proof that treatment with proteasome inhibitors stabilizes regulatory proteins (5). In this connection, we recall that the proteasome inhibitor MG132 has been found to promote StAR protein accumulation and progesterone output in cultured rat preovulatory granulosa cells (6).MG132 (Cbz-Leu-Leu-Leucin-al) is a peptide aldehyde which selectively inhibits the proteasome degradative pathway, and primarily chymotrypsin-like proteasome activity. In addition to MG132, other proteasome inhibitors are available: i) MG101 (N-Acetyl-Leu-Leu-Norleu-al), also named calpain inhibitor I; and ii) MG115 (N-Cbz-Leu-LeuNorvalin-al) (5). Therefore, it seemed worthwhile to investigate whether MG101 and MG115 influence StAR mRNA accumulation and function in rat adrenocortical cells. Materials and methods Animals and reagents. Adult female (130-140 g body weight)and 21-day-old male W...

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Section: Discussionmentioning

confidence: 99%

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

Ziolkowska¹,

Tortorella²,

Nussdorfer³

et al. 2006

Int J Mol Med

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“…the morphological preservation of tissues seemed to be insufficient to assess cytochemical data. It is well known that DMSO crosses cell membranes in a reversible manner and does not alter membrane integrity (37). We believe that the effect of DMSO may also contribute to increased permeability of membranes for the fixatives, allowing more effective penetration of the incubation medium.…”

Section: Discussionmentioning

confidence: 99%

Enzyme cytochemical study of rat cardiac muscle I. Adenylate cyclase and guanylate cyclase.

Fujimoto

Ogawa

1982

Acta Histochem. Cytochem

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“…6 It is also applied as a drug carrier to cells. 7 DMSO is one of the best cryoprotectors. 8 Due to its physicochemical properties, high solvent power, low chemical reactivity, and relatively low toxicity, DMSO is a solvent of choice for sample storage and handling in the pharmaceutical industry, particularly in stages of primary high-throughput bioscreening.…”

Section: Dmso: Properties and Role In The Pharmaceutical Industrymentioning

confidence: 99%

In Silico Estimation of DMSO Solubility of Organic Compounds for Bioscreening

Balakin¹,

Ivanenkov²,

Skorenko³

et al. 2004

SLAS Discovery

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Solubility of organic compounds in DMSO is an important issue for commercial and academic organizations handling large compound collections or performing biological screening. In particular, solubility data are critical for the optimization of storage conditions and for the selection of compounds for bioscreening compatible with the assay protocol. Solubility is largely determined by the solvation energy and the crystal disruption energy, and these molecular phenomena should be assessed in structure-solubility correlation studies. The authors summarize our long-term experimental observations and theoretical studies of physicochemical determinants of DMSO solubility of organic substances. They compiled a comprehensive reference database of proprietary data on compound solubility (55,277 compounds with good DMSO solubility and 10,223 compounds with poor DMSO solubility), calculated specific molecular descriptors (topological, electromagnetic, charge, and lipophilicity parameters), and applied an advanced machine-learning approach for training neural networks to address the solubility. Both supervised (feed-forward, back-propagated neural networks) and unsupervised (Kohonen neural networks) learning methods were used. The resulting neural network models were validated by successfully predicting DMSO solubility of compounds in independent test selections. (Journal of Biomolecular Screening 2004:22-31)

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Pharmacologic and Biochemical Considerations of Dimethyl Sulfoxide

Cited by 132 publications

References 62 publications

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

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

Enzyme cytochemical study of rat cardiac muscle I. Adenylate cyclase and guanylate cyclase.

In Silico Estimation of DMSO Solubility of Organic Compounds for Bioscreening

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