Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate

Araki, Makoto; Maeda, Masatomo; Motojima, Kiyoto

doi:10.1016/j.ejphar.2011.10.044

Cited by 54 publications

(51 citation statements)

References 25 publications

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“…autophagy in vitro, 21,22 lending credence to our hypothesis that active autophagy is the potential driving force behind colchicineinduced muscle toxicity. To explore the impact of enhanced autophagy in colchicine-induced myopathy, we evaluated muscle pathology in mice treated with rapamycin or simvastatin in the setting of colchicine.…”

Section: Introductionmentioning

confidence: 77%

“…Specifically, depletion of geranylgeranyl diphosphate by statins and bisphosphonates can induce autophagy. 21,34 Moreover, farnesyl transferase inhibitors and geranylgeranyl transferase inhibitors both induce autophagy in vitro. 35,36 Our studies confirm these cell culture models and demonstrate that statins can effectively enhance autophagic flux in vivo in mouse skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

“…Statins initiate autophagy in cultured cells. 21,33 The mechanism by which statins induce autophagy likely relates to their mechanism of action within the HMGCR pathway. Specifically, depletion of geranylgeranyl diphosphate by statins and bisphosphonates can induce autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that statins can induce autophagy in cell culture models of skeletal muscle, 21,22 but it has not been established whether this occurs in vivo in mature skeletal muscle. To evaluate this, we treated mice with four different statin drugs (simvastatin, atorvastatin, lovastatin, and pravastatin) for 7 d prior to isolating skeletal muscle and performing an immunoblot using an anti-LC3 antibody.…”

Section: Statins Induce Autophagy In Mouse Skeletal Musclementioning

confidence: 99%

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Increased autophagy accelerates colchicine-induced muscle toxicity

Ching¹,

Ju²,

Pittman³

et al. 2013

Autophagy

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Section: Introductionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Statins Induce Autophagy In Mouse Skeletal Musclementioning

confidence: 99%

See 2 more Smart Citations

Increased autophagy accelerates colchicine-induced muscle toxicity

Ching¹,

Ju²,

Pittman³

et al. 2013

Autophagy

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“…Human rhabdomyosarcoma cells are a naturally immortalized cell model, frequently used for making inferences about muscle tissue adaptations [27][28][29][30][31]. We show that treatment of muscle cells with OEP or CHD at varied doses induce PGC-1α mRNA and protein in a dose and time sensitive manner.…”

Section: Introductionmentioning

confidence: 99%

- Consumption of Fructose-Sweetened Beverages for 10 Weeks Reduces Net Fat Oxidation and Energy Expenditure in Overweight/Obese Men and Women

2015

Nutritional Biochemistry

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Background: Obesity is a common pathology with increasing incidence, and is associated with increased mortality and healthcare costs. Several treatment options for obesity are currently available ranging from behavioral modifications to pharmaceutical agents. Many popular dietary supplements claim to enhance weight loss by acting as metabolic stimulators, however direct tests of their effect on metabolism have not been performed.

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Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty

Leite

Sanabria

Cavariani

et al. 2018

J of Applied Toxicology

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The increase of obesity, bad eating habits and the lack of physical exercises are highly related to dyslipidemias. Rosuvastatin is a lipid-lowering drug and has been indicated to prevent cardiovascular diseases and to treat dyslipidemias due to its higher efficiency to reduce serum cholesterol concentrations. This study aimed to evaluate the reproductive adverse effects on sexual maturity due to rosuvastatin exposure in juvenile male rats during prepuberty. Three groups were randomly formed with newly weaned rats: control, whose rats received saline solution 0.9% and rosuvastatin at doses of 3 or 10 mg kg day , administered orally by gavage, from postnatal day 21 until preputial separation (average of 45 days for controls and 49 days for statin-treated animals), indicative of puberty onset. Male rats were maintained until sexual maturity and were killed on postnatal day 110. In the rosuvastatin-treated groups, the results showed diminished follicle-stimulating hormone, luteinizing hormone and testosterone concentrations, increased estradiol and prolactin concentrations, histopathologic alterations on testis and epididymis and decreased sperm quality. Moreover, statin-exposed groups showed decreased expression of androgen receptor on testis and epididymis and lower expression of aquaporin-9 on epididymal epithelium. In conclusion, administration of rosuvastatin to prepubertal male rats provoked long-term hormonal deregulation and impaired reproduction at adulthood.

show abstract

Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate

Cited by 54 publications

References 25 publications

Increased autophagy accelerates colchicine-induced muscle toxicity

Increased autophagy accelerates colchicine-induced muscle toxicity

- Consumption of Fructose-Sweetened Beverages for 10 Weeks Reduces Net Fat Oxidation and Energy Expenditure in Overweight/Obese Men and Women

Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty

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