Squalene synthase inhibition alters metabolism of nonsterols in rat liver

Rk, Keller

doi:10.1016/0005-2760(96)00081-1

Cited by 48 publications

(43 citation statements)

References 42 publications

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“…Song (2003) showed that disruption of sterol biosynthesis by squalene synthase resulted in a remarkable accumulation of FPP in an erg9 mutant strain of Saccharomyces cerevisiae. Besides FPP, the increase of isopentenyl diphosphate and GGPP was also observed when rat liver cells were treated with zaragozic acid, a potent inhibitor of squalene synthase (Keller, 1996). Similar effects were also observed in plants (Fulton et al, 1995).…”

Section: Discussionsupporting

confidence: 55%

Squalestatin-induced production of taxol and baccatin in cell suspension culture of yew (Taxus baccata L.)

Amini¹,

Shabani²,

Afghani³

et al. 2014

Turk J Biol

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Various elicitors have already been reported to enhance the production of taxol and related taxanes. In this study, effects of a fungal metabolite, squalestatin, on production of taxol and baccatin III were studied. Expressions of 4 key involved genes, ts, dbat, bapt, and dbtnbt, in suspension cultures of Taxus baccata were also detected using qPCR. Results showed that application of squalestatin significantly increased taxol and baccatin III yields. Increased expressions of the genes were in accordance with measures of taxol and baccatin accumulations in cells and medium. Production of H 2 O 2 has significant positive correlations with both gene expression and taxanes, indicating that the increase in H 2 O 2 might be involved in the upregulation of the taxane production in yew under squalestatin treatment. Our results suggest that H 2 O 2 is a key signaling component in the stimulation of taxane production in T. baccata cells induced by squalestatin.

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Section: Discussionsupporting

confidence: 55%

Squalestatin-induced production of taxol and baccatin in cell suspension culture of yew (Taxus baccata L.)

Amini¹,

Shabani²,

Afghani³

et al. 2014

Turk J Biol

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“…SQS inhibitors increase farnesol and farnesol-derived dicarboxylic acids in vitro (17), and an increase was also reported in mice, rats, and beagle dogs (4,(18)(19)(20). To study the effects of farnesol and its derivatives on triglyceride biosynthesis, we added 100 M farnesol, squalene, farnesyl acetate, 3,7,11-trimethyl-2,6,10-dodecatriene-1,12-dioic acid methylester, 3,7-dimethyl-2,6-decadiene-1,10-dioic acid methylester, 3,7-dimethyl-2,6-octadiene-1,8-dioic acid methylester, 3-methyl-2-hexamonoene-1,6-dioic acid methylester, and suberic acid to hepatocytes, and evaluated their ability to inhibit triglyceride biosynthesis ( Fig.…”

Section: Effect Of Farnesol and Its Derivatives On Lipid Biosynthesismentioning

confidence: 77%

“…It was reported that inhibition of SQS increased farnesol levels in cultured cells (17). In animal experiments, SQS inhibitors increased farnesol and farnesol-derived dicarboxylic acids in liver tissues (4,18,19). Bostedor and colleagues identified common dicarboxylic acids that were increased in urine of rats and dogs treated with either zaragozic acid A, a SQS inhibitor, or farnesol (20).…”

Section: Discussionmentioning

confidence: 99%

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Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes

Hiyoshi

Yanagimachi

Ito

et al. 2003

Journal of Lipid Research

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“…Among the hormones, thyroxine induces hepatic biosynthesis of CoQ and may be responsible for the elevated level of this lipid in the livers of rodents maintained at 4°C for 10 days (36, 37). Furthermore, both vitamin A deficiency and inhibition of squalene synthase by squalestatin 1 lead to elevated levels of CoQ in both cultured cells and rats (38,39).…”

Section: Discussionmentioning

confidence: 99%

Polyisoprenoid Epoxides Stimulate the Biosynthesis of Coenzyme Q and Inhibit Cholesterol Synthesis

Bentinger

Tekle

Brismar

et al. 2008

Journal of Biological Chemistry

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In our search for compounds that up-regulate the biosynthesis of coenzyme Q (CoQ), we discovered that irradiation of CoQ with ultraviolet light results in the formation of a number of compounds that influence the synthesis of mevalonate pathway lipids by HepG2 cells. Among the compounds that potently stimulated CoQ synthesis while inhibiting cholesterol synthesis, derivatives of CoQ containing 1-4 epoxide moieties in their polyisoprenoid side chains were identified. Subsequently, chemical epoxidation of all-trans-polyprenols of different lengths revealed that the shorter farnesol and geranylgeraniol derivatives were without effect, whereas the longer derivatives of solanesol enhanced CoQ and markedly reduced cholesterol biosynthesis. In contrast, none of the modified trans-transpoly-cis-polyprenols exerted noticeable effects. Tocotrienol epoxides were especially potent in our system; those with one epoxide moiety in the side-chain generally up-regulated CoQ biosynthesis by 200 -300%, whereas those with two such moieties also decreased cholesterol synthesis by 50 -90%. Prolonged treatment of HepG2 cells with tocotrienol epoxides for 26 days elevated their content of CoQ by 30%. In addition, the levels of mRNA encoding enzymes involved in CoQ biosynthesis were also elevated by the tocotrienol epoxides. The site of inhibition of cholesterol synthesis was shown to be oxidosqualene cyclase. In conclusion, epoxide derivatives of certain all-trans-polyisoprenoids cause pronounced stimulation of CoQ synthesis and, in some cases, simultaneous reduction of cholesterol biosynthesis by HepG2 cells.

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Squalene synthase inhibition alters metabolism of nonsterols in rat liver

Cited by 48 publications

References 42 publications

Squalestatin-induced production of taxol and baccatin in cell suspension culture of yew (Taxus baccata L.)

Squalestatin-induced production of taxol and baccatin in cell suspension culture of yew (Taxus baccata L.)

Squalene synthase inhibitors suppress triglyceride biosynthesis through the farnesol pathway in rat hepatocytes

Polyisoprenoid Epoxides Stimulate the Biosynthesis of Coenzyme Q and Inhibit Cholesterol Synthesis

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