Protein Information

Name cytochrome P450 (protein family or complex)
Synonyms cytochrome P450; cytochrome P 450; CYP450; CYP 450

Compound Information

Name rotenone
CAS

Reference List

PubMed Abstract RScore(About this table)
9500851 Shimada H, Hirai K, Simamura E, Pan J: Mitochondrial NADH-quinone oxidoreductase of the outer membrane is responsible for paraquat cytotoxicity in rat livers. Arch Biochem Biophys. 1998 Mar 1;351(1):75-81.


The outer membrane fractions, free from the contamination of inner membranes but with a few microsomes, catalyzed rotenone-insensitive NADH, but not NADPH, oxidation by menadione or PQ.
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9282833 Fang N, Rowlands JC, Casida JE: Anomalous structure-activity relationships of 13-homo-13-oxarotenoids and 13-homo-13-oxadehyrorotenoids. Chem Res Toxicol. 1997 Aug;10(8):853-8.


Cube resin, used as an insecticide/miticide and piscicide, contains in decreasing amounts rotenone (1), deguelin (2), the 6a,12a-dehydro derivatives of rotenone (3) and deguelin (4), and the newly-discovered 13-homo-13-oxa-6a,12a-dehydro analogs [referred to as oxadehydrorotenone (5) and -deguelin (6)].
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9258337 Tang DG, Honn KV: Apoptosis of W256 carcinosarcoma cells of the monocytoid origin induced by NDGA involves lipid peroxidation and depletion of GSH: role of 12-lipoxygenase in regulating tumor cell survival. J Cell Physiol. 1997 Aug;172(2):155-70.


W256 cell apoptosis induced by NDGA could also be effectively inhibited by GSH-elevating or thiol agents as well as by lipid peroxidation inhibitors and an inhibitor of mitochondria respiratory chain rotenone.
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17172037 Ren SZ, Guo J, Cen YH, Sun GP: [Properties of a triphenylmethane dyes decolorization enzyme (TpmD) from Aeromonas hydrophila strain DN322]. Wei Sheng Wu Xue Bao. 2006 Oct;46(5):823-6.


Based on previous results, the effect of different inhibitor including Vc, metyrapone, rotenone, antimycin A and NaN3 as well as the effect of FAD and FMN on the activity of TpmD were measured.
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2825631 Tomasi A, Albano E, Banni S, Botti B, Corongiu F, Dessi MA, Iannone A, Vannini V, Dianzani MU: Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. Biochem J. 1987 Sep 1;246(2):313-7.


The addition of inhibitors of the respiratory chain such as antimycin A and KCN decreased free-radical formation by only 30%, whereas rotenone displayed a greater effect (approx. 84% inhibition), but only when preincubated for 15 min with mitochondria not supplemented with succinate.
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8836123 O'Donnell VB, Azzi A: High rates of extracellular superoxide generation by cultured human fibroblasts: involvement of a lipid-metabolizing enzyme. Biochem J. 1996 Sep 15;318 ( Pt 3):805-12.


Inhibitor studies showed that there was no involvement of NADPH oxidase (diphenylene iodonium, diphenyl iodonium), prostaglandin H synthase (indomethacin), xanthine oxidase (allopurinol), cytochrome P-450 (metyrapone) or mitochondrial respiration (rotenone, antimycin A).
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8648915 Zager RA: Mitochondrial free radical production induces lipid peroxidation during myohemoglobinuria. Kidney Int. 1996 Mar;49(3):741-51.


Site 2 (antimycin A) or site 3 (cyanide, hypoxia) mitochondrial respiratory chain inhibition completely blocked lipid peroxidation, whereas site 1 inhibition (rotenone) doubled its extent (presumably by shunting NADH through NADH dehydrogenase, a free radical generating system).
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6378256 Ryder NS, Dupont MC: Properties of a particulate squalene epoxidase from Candida albicans. Biochim Biophys Acta. 1984 Jul 26;794(3):466-71.


Epoxidase activity was destroyed by Triton X-100, deoxycholate or Cu2+, and partially inhibited by thiol reagents, rotenone and antimycin A.
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7529030 Zulueta JJ, Yu FS, Hertig IA, Thannickal VJ, Hassoun PM: Release of hydrogen peroxide in response to hypoxia-reoxygenation: role of an NAD (P) H oxidase-like enzyme in endothelial cell plasma membrane. Am J Respir Cell Mol Biol. 1995 Jan;12(1):41-9.


Furthermore, inhibitors of cyclooxygenase (indomethacin), phospholipase A2 (quinacrine and chlorpromazine), nitric oxide synthase (L-arginine analogs), the mitochondrial electron transport chain (rotenone and cyanide), and cytochrome P-450 (methoxypsoralen) had no or minimal effect on this release.
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16325340 Kotze AC, Dobson RJ, Chandler D: Synergism of rotenone by piperonyl butoxide in Haemonchus contortus and Trichostrongylus colubriformis in vitro: potential for drug-synergism through inhibition of nematode oxidative detoxification pathways. Vet Parasitol. 2006 Mar 31;136(3-4):275-82. Epub 2005 Dec 1.

The anthelmintic properties of rotenone and its activity in combination with the cytochrome P450 inhibitor piperonyl butoxide, were examined in in vitro assays with adults and larvae of Haemonchus contortus and larvae of Trichostrongylus colubriformis.
62(0,2,2,2) Details
19781192 Chen Y, Zhang AH, Huang SM, Ding GX, Zhang WZ, Bao HY, Wu HM, Chen RH: [NADPH oxidase-derived reactive oxygen species involved in angiotensin II-induced monocyte chemoattractant protein-1 expression in mesangial cells]. Zhonghua Bing Li Xue Za Zhi. 2009 Jul;38(7):456-61.

In contrast, inhibitors of other oxidant-producing enzymes, including the mitochondrial complex Iinhibitor rotenone, the xanthine oxidase inhibitor allopurinol, the cyclooxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguiaretic acid, the cytochrome P450 oxygenase inhibitor ketoconazole and the nitric oxide synthase inhibitor G-nitro-L-arginine methyl ester were without an effect.
31(0,1,1,1) Details
17881465 Ding G, Zhang A, Huang S, Pan X, Zhen G, Chen R, Yang T: ANG II induces c-Jun NH2-terminal kinase activation and proliferation of human mesangial cells via redox-sensitive transactivation of the EGFR. Am J Physiol Renal Physiol. 2007 Dec;293(6):F1889-97. Epub 2007 Sep 19.

In contrast, inhibitors of other oxidant-producing enzymes, including the mitochondrial complex I inhibitor rotenone, the xanthine oxidase inhibitor allopurinol, the cyclooxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguiaretic acid, the cytochrome P-450 oxygenase inhibitor ketoconazole, and the nitric oxide synthase inhibitor N (G)-nitro-l-arginine methyl ester, were without effect.
31(0,1,1,1) Details
7318685 Grafstom R, Stohs SJ: Inhibitors of 7-ethoxyresorufin and 7-ethoxycoumarin de-ethylases in rat small intestinal microsomes and cells. Drug Chem Toxicol. 1981;4(2):147-59.

These results, in conjunction with previous investigations, suggest that rotenone and ANF may be most useful in differentiating between various species of cytochrome P-450.
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3259740 Erickson DA, Goodrich MS, Lech JJ: The effect of piperonyl butoxide on hepatic cytochrome P-450-dependent monooxygenase activities in rainbow trout (Salmo gairdneri). Toxicol Appl Pharmacol. 1988 Jun 15;94(1):1-10.

Treatment of trout with PBO in a flow-through system resulted in an increase in ECOD and EROD activity in hepatic microsomes while simultaneously decreasing their activity toward [14C] rotenone oxidation.
4(0,0,0,4) Details
9067905 Zager RA, Burkhart K: Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. Kidney Int. 1997 Mar;51(3):728-38.

Blockade of site 2 (antimycin) and site 3 (azide), but not site 1 (rotenone), mitochondrial electron transport significantly reduced myoglobin cytotoxicity.
The roles played by heme oxygenase (HO), cytochrome p450, free iron, intracellular Ca2+, nitric oxide, H2O2, hydroxyl radical (-OH), and mitochondrial electron transport were assessed.
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7192358 Il'chenko AP, Sokolov GV: [Effect of inhibitors of microsomal hydroxylation on endogenous respiration of Torulopsis candida cells]. Mikrobiologiia. 1980 Sep-Oct;49(5):664-8.

The effect of inhibitors of microsomal cytochrome P-450 on endogenous respiration and the redox state of components in the electron transport chain was studied in the cells of Torulopsis candida.
Contrary to their action on endogenous respiration of the cells at the exponential phase, both benzhydroxamic acid (BHA) and the inhibitors of microsomal hydroxylation, in the presence of rotenone, suppressed endogenous respiration of the cells taken at the stationary phase.
3(0,0,0,3) Details
3281665 Hagenfeldt Y, Pedersen JI, Bjorkhem I: Properties of guinea-pig kidney 25-hydroxyvitamin D3 1 alpha-hydroxylase assayed by isotope dilution-mass spectrometry. Biochem J. 1988 Mar 1;250(2):521-6.

Mitochondrial respiratory-chain inhibitors (cyanide, rotenone, antimycin A) had no effect on the hydroxylation.
CO had an inhibitory effect, suggesting participation of a species of cytochrome P-450 in the reaction.
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2764708 Catinot R, Hoellinger H, Sonnier M, Do-Cao-Thang, Pichon J, Nguyen-Hoang-Nam: In vitro covalent binding of the pyrethroids cismethrin, cypermethrin and deltamethrin to rat liver homogenate and microsomes. Arch Toxicol. 1989;63(3):214-20.

With liver homogenate, inhibition of esterases by tetraethylpyrophosphate and of mitochondrial respiration by rotenone or potassium cyanide only slightly altered the covalent binding level.
With microsomes, inhibition of cytochrome P-450 and mixed function oxidases by carbon monoxide and piperonyl butoxide reduced the covalent binding so far as to be nearly absent.
2(0,0,0,2) Details
6802189 Chistiakov VV, Pospelova LN: [Transport of electrons from mitochondria to microsomes in the reconstituted system of cell organelles]. Biokhimiia. 1982 Jan;47(1):55-61.

The reduction of cytochrome P-450--CO complex in the presence of various agents in the reconstituted system of liver cell organelles was studied.
The addition of glutamate (but not succinate), NAD+ and amytal (or rotenone) to the reconstituted system caused a 40-50% reduction of NADPH-reducible cytochrome P-450.
2(0,0,0,2) Details
181251 Uemura T, Chiesara E: NADH-dependent aryl hydrocarbon hydroxylase in rat liver mitochondrial outer membrane. Eur J Biochem. 1976 Jul 1;66(2):293-307.


The hydroxylase system is composed of cyanide-insensitive cytochrome P-450 and is inducible markedly by 3-methylcholanthrene treatment.
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3355535 Pedersen JI, Hagenfeldt Y, Bjorkhem I: Assay and properties of 25-hydroxyvitamin D3 23-hydroxylase. Biochem J. 1988 Mar 1;250(2):527-32.

These results indicate that the guinea-pig renal mitochondrial 23-hydroxylase is a cytochrome P-450 and that the reducing equivalents are primarily supplied by NADPH via the energy-dependent transhydrogenase.
It was stimulated by the respiratory-chain inhibitors rotenone, antimycin A and KCN.
1(0,0,0,1) Details
6600452 Pedersen JI, Shobaki HH, Holmberg I, Bergseth S, Bjorkhem I: 25-Hydroxyvitamin D3-24-hydroxylase in rat kidney mitochondria. . J Biol Chem. 1983 Jan 25;258(2):742-6.

Low O2 tension, CO, KCN, and the uncoupler carbonyl cyanide m-chlorophenylhydrazone inhibited the reaction, while the respiratory inhibitor rotenone had no effect.
The results indicate that in the rat the renal mitochondrial 25-hydroxyvitamin D3-24-hydroxylase is a cytochrome P-450 and that the reducing equivalents are primarily supplied by NADPH via the energy-dependent transhydrogenase.
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4401048 Ichikawa Y, Loehr JS: NADH-dependent cytochrome P-450 oxidase system in submicrosomal particles. Biochem Biophys Res Commun. 1972 Feb 16;46(3):1187-93.

1(0,0,0,1) Details
9644252 Matsunaga I, Yamada M, Kusunose E, Miki T, Ichihara K: Further characterization of hydrogen peroxide-dependent fatty acid alpha-hydroxylase from Sphingomonas paucimobilis. J Biochem. 1998 Jul;124(1):105-10.

Other respiratory chain inhibitors such as rotenone and antimycin A did not inhibit the activity.
Among cytochrome P450 inhibitors, SKF-525A markedly inhibited the activity at the concentration of 2 mM, but CO did not.
1(0,0,0,1) Details
4842299 von Bahr C, Vadi H, Grundin R, Moldeus P, Orrenius S: Spectral studies on the rapid uptake and subsequent binding of drugs to cytochrome P-450 in isolated rat liver cells. Biochem Biophys Res Commun. 1974 Jul 10;59(1):334-9.

1(0,0,0,1) Details
6289887 Bindoli A, Cavallini L, Jocelyn P: Mitochondrial lipid peroxidation by cumene hydroperoxide and its prevention by succinate. Biochim Biophys Acta. 1982 Sep 15;681(3):496-503.

Mitochondrial lipid peroxidation by cumene hydroperoxide is strongly inhibited by SKF52A (an inhibitor of cytochrome P-450), by antioxidants and to a lesser extent by the enzymes superoxide dismutase and catalase.
Conversely, rotenone and N-ethylmaleimide stimulate the reaction.
1(0,0,0,1) Details
1540380 Kinnula VL, Whorton AR, Chang LY, Crapo JD: Regulation of hydrogen peroxide generation in cultured endothelial cells. . Am J Respir Cell Mol Biol. 1992 Feb;6(2):175-82.

Endogenous hydrogen peroxide (H2O2) release from aortic endothelial cells was studied in the presence of antioxidant enzyme inhibitors, mitochondrial inhibitors, a microsomal cytochrome P-450 inhibitor, and after oxidative stress induced with H2O2 or menadione.
Furthermore, inhibition of the mitochondrial respiratory chain (rotenone, antimycin A) or microsomal cytochrome P-450 (8-methoxypsoralen) did not change extracellular H2O2 release or intracellular H2O2 production (at peroxisomes) by endothelial cells or cells in which glutathione reductase was inactivated.
1(0,0,0,1) Details
12704789 Albright CD, Salganik RI, Craciunescu CN, Mar MH, Zeisel SH: Mitochondrial and microsomal derived reactive oxygen species mediate apoptosis induced by transforming growth factor-beta1 in immortalized rat hepatocytes. J Cell Biochem. 2003 May 15;89(2):254-61.

Therefore, our studies indicate that concurrent with promoting generation of ROS from mitochondria, TGFbeta1 also promotes generation of ROS from the cytochrome P450 electron transfer chain.
A similar effect was obtained by treating these cells with rotenone, an inhibitor of complex 1 of the mitochondrial electron transfer chain.
1(0,0,0,1) Details
9185043 Zhao C, Xiong Y, Shichi H: Acetaminophen cytotoxicity in mouse eye: mitochondria in anterior tissues are the primary target. J Ocul Pharmacol Ther. 1997 Jun;13(3):269-76.

Acetaminophen (APAP) injected into C57BL/6 mice (cytochrome P450 inducer-responsive strain) that had been pretreated with b-naphthoflavone (BNF) produced ocular tissue damage, including cataract.
The oxygen uptake was inhibited about 50% by 10 microM rotenone.
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2996532 Niranjan BG, Avadhani NG, DiGiovanni J: Formation of benzo (alpha) pyrene metabolites and DNA adducts catalyzed by a rat liver mitochondrial monooxygenase system. Biochem Biophys Res Commun. 1985 Sep 16;131(2):935-42.

The mitoplasts used in this study contained less than 1% microsomal marker enzymes: rotenone insensitive NADPH cytochrome c reductase and glucose-6-phosphatase.
The rates of BaP metabolism and DNA adduct formation per nanomole cytochrome P-450 were different for MCA induced mitochondrial and microsomal enzymes.
1(0,0,0,1) Details
4152752 Moldeus P, Grundin R, Vadi H, Orrenius S: A study of drug metabolism linked to cytochrome P-450 in isolated rat-liver cells. Eur J Biochem. 1974 Jul 15;46(2):351-60.

1(0,0,0,1) Details
19278021 Song C, Scharf ME: Mitochondrial impacts of insecticidal formate esters in insecticide-resistant and insecticide-susceptible Drosophila melanogaster. Pest Manag Sci. 2009 Jun;65(6):697-703.

These studies compared two Drosophila strains: an insecticide-susceptible strain (Canton-S) and a strain resistant by cytochrome P450 overexpression (Hikone-R).
Formic acid and three positive control treatments (rotenone, antimycin A and sodium cyanide) induced cytochrome c release, verifying that formic acid is capable of causing mitochondrial disruption.
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1149022 Vadi H, Moldeus P, Capdevila J, Orrenius S: The metabolism of benzo (alpha) pyrene in isolated rat liver cells. Cancer Res. 1975 Aug;35(8):2083-91.


The pattern of metabolites of BP was the same in isolated rat liver cells and in the isolated perfused rat liver. 3-Methylcholanthrene treatment of the rats caused a marked increase in cellular BP metabolism as well as in cytochrome P-450 concentration.
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8932536 Espinosa-Garcia MT, Martinez F: Presence of an NAD (P) H dehydrogenase and A b-type cytochrome different from the respiratory chain in submitochondrial particles from human placenta. Biochem Mol Biol Int. 1996 Feb;38(1):205-14.


The results suggest a connection between the respiratory chain and cytochrome P450, through an NAD (P) H-DH and a b-type cytochrome, both different from the respiratory chain.
1(0,0,0,1) Details
167532 Bartoli GM, Dani A, Galeotti T, Russo M, Terranova T: Respiratory activity of Ehrlich ascites tumour cell nuclei. . Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1975;83(3):223-31.


These nuclei contain cytochrome b5, whereas cytochrome P-450 or mitochondrial-like cytochromes are lacking. 4.
1(0,0,0,1) Details
3453688 Bindoli A, Valente M, Cavallini L: Prevention of lipid peroxidation by NAD (P) H in rat liver submitochondrial particles. Biochem Int. 1987 Jul;15(1):255-62.

Rotenone slightly prevents both the protective effect on malondialdehyde formation and peroxidase activity.
The peroxidase activity of rat liver submitochondrial particles was attributed to the NAD (P) H-mediated reduction of mitochondrial cytochrome P-450 which can act upon hydroperoxides, by decomposing them to alcohols.
1(0,0,0,1) Details
223663 Comte J, Gautheron DC: The markers of pig heart mitochondrial sub-fractions : I. - The dual location of NADPH-cytochrome c reductase in outer membrane and microsomes. Biochimie. 1978;60(11-12):1289-98.

Mitochondrial outer membrane differs from microsomes by a low choline phosphotransferase activity and the absence of cytochrome P-450.
The properties of mitochondrial and microsomal rotenone-insensitive NADH- and NADPH-cytochrome c reductases were studied.
1(0,0,0,1) Details
47760 Olivera AA, Meigs RA: Mitochondria from human term placenta. Biochim Biophys Acta. 1975 Mar 20;376(3):436-45.

Inhibition by rotenone, antimycin A and cyanide established the classical electron transport chain as the major pathway of respiration with glutamate and succinate as substrates.
Approximately 20% of glutamate-supported respiration was insensitive to inhibitors and may proceed by the cytochrome P-450 linked pathway of electron transport.
1(0,0,0,1) Details
7646435 O'Donnell VB, Spycher S, Azzi A: Involvement of oxidants and oxidant-generating enzyme (s) in tumour-necrosis-factor-alpha-mediated apoptosis: role for lipoxygenase pathway but not mitochondrial respiratory chain. Biochem J. 1995 Aug 15;310 ( Pt 1):133-41.

Using specific inhibitors, we ruled out involvement of several oxidant-generating enzymes [cyclo-oxygenase (indomethacin), cytochrome P-450 (metyrapone), nitric oxide synthase (NG-methyl-L-arginine), NADPH oxidase (iodonium diphenyl), xanthine oxidase (allopurinol), ribonucleotide reductase (hydroxyurea)] in TNF alpha-mediated apoptosis of the murine fibrosarcoma line, L929.
We also demonstrated no role for mitochondrial-derived radicals/respiratory chain in the lytic pathway using specific inhibitors/uncouplers (rotenone, KCN, carboxin, fluoroacetate, antimycin, malonate, carbonyl cyanide p-trifluoromethoxyphenylhydrazone) and chloramphenicol-derived respiration-deficient cells.
1(0,0,0,1) Details
16531806 Lijnen P, Papparella I, Petrov V, Semplicini A, Fagard R: Angiotensin II-stimulated collagen production in cardiac fibroblasts is mediated by reactive oxygen species. J Hypertens. 2006 Apr;24(4):757-66.


Rotenone, allopurinol, indomethacin, nordihydroguiaretic acid, ketoconazole and nitro-L-arginine (inhibitors of mitochondrial NAD (P) H oxidase, xanthine oxidase, cyclooxygenase, lipoxygenase, cytochrome P450 oxygenase and nitric oxide synthase, respectively) did not affect the angiotensin II-induced collagen production.
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10967318 Tirmenstein MA, Nicholls-Grzemski FA, Zhang JG, Fariss MW: Glutathione depletion and the production of reactive oxygen species in isolated hepatocyte suspensions. Chem Biol Interact. 2000 Jul 14;127(3):201-17.


In agreement with this conclusion, mitochondrial electron transport inhibitors (rotenone, thenoyltrifluoroacetone and antimycin A) increased EMS-induced lipid peroxidation and cell death, while the mitochondrial uncoupler, carbonyl cyanide m-chlorophenylhydrazone, blocked EMS- and DEM-mediated ROS production and lipid peroxidation.
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14732287 Herrera B, Murillo MM, Alvarez-Barrientos A, Beltran J, Fernandez M, Fabregat I: Source of early reactive oxygen species in the apoptosis induced by transforming growth factor-beta in fetal rat hepatocytes. Free Radic Biol Med. 2004 Jan 1;36(1):16-26.


Rotenone, an inhibitor of the NADH dehydrogenase in mitochondrial complex I, attenuated, but did not completely inhibit, ROS-production, caspase activation, and cell death mediated by TGF-beta.
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