RGD Reference Report - ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. - Rat Genome Database

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ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome.

Authors: Schneider, JG  Finck, BN  Ren, J  Standley, KN  Takagi, M  Maclean, KH  Bernal-Mizrachi, C  Muslin, AJ  Kastan, MB  Semenkovich, CF 
Citation: Schneider JG, etal., Cell Metab. 2006 Nov;4(5):377-89.
RGD ID: 1601248
Pubmed: PMID:17084711   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cmet.2006.10.002   (Journal Full-text)

Metabolic syndrome is associated with insulin resistance and atherosclerosis. Here, we show that deficiency of one or two alleles of ATM, the protein mutated in the cancer-prone disease ataxia telangiectasia, worsens features of the metabolic syndrome, increases insulin resistance, and accelerates atherosclerosis in apoE-/- mice. Transplantation with ATM-/- as compared to ATM+/+ bone marrow increased vascular disease. Jun N-terminal kinase (JNK) activity was increased in ATM-deficient cells. Treatment of ATM+/+apoE-/- mice with low-dose chloroquine, an ATM activator, decreased atherosclerosis. In an ATM-dependent manner, chloroquine decreased macrophage JNK activity, decreased macrophage lipoprotein lipase activity (a proatherogenic consequence of JNK activation), decreased blood pressure, and improved glucose tolerance. Chloroquine also improved metabolic abnormalities in ob/ob and db/db mice. These results suggest that ATM-dependent stress pathways mediate susceptibility to the metabolic syndrome and that chloroquine or related agents promoting ATM activity could modulate insulin resistance and decrease vascular disease.




  
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Original Reference(s)
AtmMouseMetabolic Syndrome  IDA  RGD 
AtmRatMetabolic Syndrome  ISOAtm (Mus musculus) RGD 


Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)