PMID- 19419245
OWN - NLM
STAT- MEDLINE
DCOM- 20090825
LR  - 20171116
IS  - 1557-8577 (Electronic)
IS  - 1549-1684 (Linking)
VI  - 12
IP  - 2
DP  - 2009 Apr
TI  - Stimulation of autophagy by antilipolytic drugs may rescue rodents from 
      age-associated hypercholesterolemia.
PG  - 77-84
LID - 10.1089/rej.2008.0806 [doi]
AB  - Aging is characterized by several metabolic changes responsible for the decline 
      of certain functions and the appearance of age-related diseases, including 
      hypercholesterolemia, which is the main risk factor for atherosclerosis and 
      cardiovascular disease. Similar changes in a number of morphological and 
      biochemical parameters were observed in rats. Caloric restriction (CR) was shown 
      to increase longevity and prevent age-related diseases in various organisms, and 
      to counteract the age-associated increase in plasma cholesterol. CR was thought 
      to operate through the stimulation of the process of macroautophagy. The aim of 
      this work was to investigate the effect of the stimulation of macroautophagy on 
      age-associated cholesterolemia. Mature Sprague-Dawley rats were fasted overnight 
      and given the antilipolytic agent 3,5-dimethylpyrazole (DMP; 12 mg/kg b.w. in 0.2 
      mL of saline, intraperitoneally). The age-related changes in cholesterol plasma 
      level, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R) activity, and 
      lipoperoxidation were determined. Low-density lipoprotein (LDL) receptor 
      expression was determined by immunoblot of sodium dodecyl sulfate polyacrylamide 
      gel electrophoresis (SDS-PAGE)-separated liver membranes. Results show that the 
      stimulation of macroautophagy reduces the total LDL and high-density lipoprotein 
      (HDL) cholesterol plasma level to juvenile values, and triglycerides levels even 
      lower. The hypocholesterolemic action of DMP requires neither the counteraction 
      of the age-related changes in the HMG-CoA-R activation state and regulation, nor 
      the counteraction of the age-related increase in lipoperoxidation, and only 
      involves a restoration of the numbers of LDL receptors on liver membranes to 
      juvenile levels.
FAU - Straniero, Sara
AU  - Straniero S
AD  - Centro di Ricerca di Biologia e Patologia dell'Invecchiamento, Universita di 
      Pisa, Pisa, Italy.
FAU - Cavallini, Gabriella
AU  - Cavallini G
FAU - Donati, Alessio
AU  - Donati A
FAU - Pallottini, Valentina
AU  - Pallottini V
FAU - Martini, Chiara
AU  - Martini C
FAU - Trentalance, Anna
AU  - Trentalance A
FAU - Bergamini, Ettore
AU  - Bergamini E
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Rejuvenation Res
JT  - Rejuvenation research
JID - 101213381
RN  - 0 (Amino Acids, Branched-Chain)
RN  - 0 (Cell Extracts)
RN  - 0 (Lipids)
RN  - 0 (Pyrazoles)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, LDL)
RN  - EC 1.1.1.- (Hydroxymethylglutaryl CoA Reductases)
RN  - H21N865K9J (3,5-dimethylpyrazole)
SB  - IM
MH  - Aging/blood/*drug effects/*pathology
MH  - Amino Acids, Branched-Chain/blood
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Extracts
MH  - Enzyme Activation/drug effects
MH  - Hydroxymethylglutaryl CoA Reductases/metabolism
MH  - Hypercholesterolemia/blood/enzymology/*prevention & control
MH  - Injections, Intraperitoneal
MH  - Lipids/blood
MH  - Lipolysis/*drug effects
MH  - Liver/drug effects/enzymology
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Pyrazoles/administration & dosage/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, LDL/metabolism
MH  - Time Factors
EDAT- 2009/05/08 09:00
MHDA- 2009/08/26 09:00
CRDT- 2009/05/08 09:00
PHST- 2009/05/08 09:00 [entrez]
PHST- 2009/05/08 09:00 [pubmed]
PHST- 2009/08/26 09:00 [medline]
AID - 10.1089/rej.2008.0806 [doi]
PST - ppublish
SO  - Rejuvenation Res. 2009 Apr;12(2):77-84. doi: 10.1089/rej.2008.0806.