Anisomycin

Anisomycin is a potent protein synthesis inhibitor which interferes with protein and DNA synthesis by inhibiting peptidyl transferase or the 80S ribosome system.

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Research Areas >> Cancer

DNA synthesis[1]

To examine whether JNK has a core role in colistin-induced neurotoxicity in PC-12 cells, an SP600125 (a highly selective inhibitor of JNK) and Anisomycin (a potent activator) are used in this study. In order to select an appropriate concentration, PC-12 cells are treated with a range of SP600125 (0-80 μM) and Anisomycin (0-20 μM) respectively for 24 h. The results show that the cells viability significantly decreases by SP600125 treatment in a concentration-dependent manner, observed at the concentrations greater than 20 μM (p<0.01). Similarly the cells viability is inhibited by Anisomycin treatment (≥8 μM) (p<0.05) [1].

Disruption of TNFRp55/p75 attenuates Anisomycin-induced ventricular functional improvements. Anisomycin results in an improvement in left ventricular developed pressure (LVDP), which disappears in animals with disruption of TNFR p55/p75. In addition, the Anisomycin-induced improvement in LVEDP in wild-type animals is eliminated by deletion of TNFR p55/p75. Likewise, disruption of TNFR p55/p75 abrogates the recovery of rate pressure product (RPP) elicited by pretreatment of Anisomycin. TNFR p55/p75-/- mice without Anisomycin treatment do not show differences in cardiac functional recovery compared with the control wild-type mice. There are no significant differences in heart rate between wild-type and TNFR p55/p75-deficient mice. To see whether Nox2 is involved in Anisomycin-induced myocardial protection, Nox2-deficient mice are treated with Anisomycin. The improvement in the LVEDP in Anisomycin-treated mice is eliminated in Nox2-/- mice compared with wild-type mice. In addition, recovery of RPP in wild-type mice treated with Anisomycin is mitigated in Nox2-/- mice. Nox2-/- mice without Anisomycin treatment do not show the difference in cardiac functional recovery compared with wild-type control mice[2].

PC-12 cells are seeded in 96-well plates at a concentration of 1×104 cells/well and cultured in an incubator at 37°C with 5% CO2 for at least 12 h prior to exposure to different concentrations of SP600125 (0-80 μM) or Anisomycin (0-20 μM) for 24 h. Subsequently, the culture medium is added to 20 μL of 5 mg/mL MTT working solution and the plate is incubated for 2 h at 37°C. The culture supernatant is removed and the formazan crystals are dissolved in 150 μL DMSO. Finally, the absorbance of each well is measured at 490 nm by a microplate reader. Cell viability is expressed as the percentage of the control group, which is set to 100%[1].

Mice[2] Adult male TNFRp55/p75 mice, adult male wild-type C57/BL and homozygous Nox2-/- mice are used in this study. Mice are randomized into six experimental groups that undergo the following treatments,. Animals are divided into six groups: group 1: control ischemia/reperfusion, wild-type mice are injected with DMSO (0.1 mL); group 2: Anisomycin+wild-type mice, wild-type mice are injected with Anisomycin (0.1 mg/kg ip); group 3: Anisomycin+TNFR p55/p75-/- mice, TNFR p55/75-/- mice are injected with Anisomycin (0.1 mg/kg ip); group 4: TNFR p55/p75-/- mice, TNFR p55/75-/- mice are not injected with Anisomycin; group 5: Anisomycin+Nox2-/- mice, Nox2-/- mice are injected with Anisomycin (0.1 mg/kg ip); and group 6: Nox2-/- mice, Nox2-/- mice are not injected with Anisomycin. Later (24 h), the hearts are subjected to 30 min of ischemia followed by 30 min of reperfusion[2].

[1]. Lu Z, et al. Colistin-induced autophagy and apoptosis involves the JNK-Bcl2-Bax signaling pathway and JNK-p53-ROS positive feedback loop in PC-12 cells.

[2]. Zhao TC, et al. Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by Anisomycin. Am J Physiol Heart Circ Physiol. 2012 Nov 15;303(10):H1263-72.

Cycloheximide | Actinomycin D | alpha-Amanitin | SCR7 | CX-5461 | LMI070 | COH29 | Triciribine | Folic Acid | Halofuginone | RG7800 | ML216 | Adenine | Nedaplatin | Triapine

DATA ITEMS CITED :

18

MOLECULAR FORMULA :

C14-H19-N-O4

MOLECULAR WEIGHT :

265.34

WISWESSER LINE NOTATION :

T5MTJ B1R DO1& COV1 DQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

72 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

345 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

230 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

167 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

148 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

10 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

85GDA2 "CRC Handbook of Antibiotic Compounds," Vols.1- , Berdy, J., Boca Raton, FL, CRC Press, 1980- Volume(issue)/page/year: 5,77,1981

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>300 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>100 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>100 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

>300 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

>50 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

>200 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

>200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 5,490,1955 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5265 No. of Facilities: 63 (estimated) No. of Industries: 1 No. of Occupations: 4 No. of Employees: 504 (estimated) No. of Female Employees: 420 (estimated)