Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menopause is associated with an increased risk of cardiovascular disease (CVD). Exercise and soy isoflavone diets have been suggested to reduce the risk of CVD in postmenopausal women. We investigated the effects of exercise, or combined exercise and soy isoflavone diet, on plasma lipid profiles, paraoxonase (PON), nitric oxide (NO) and apoptosis in the aorta of ovariectomized (OVX) rats. Thirty-two female Sprague-Dawley rats were divided into four groups: OVX with general diet (OVX-GD), OVX with isoflavone diet (OVX-ISO), OVX-GD with exercise training (OVX-ET) and OVX-ISO with exercise training (OVX-ISO+ET). The experimental rats undertook treadmill training (30 min/day, 4 days/week) and/or were supplied a soy isoflavone diet (added to the experimental diet at 2.39 mg/g protein) for 12 weeks. Body weight and levels of total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C) increased in the OVX rats and HDL-C decreased. These effects were reduced by exercise and/or soy isoflavone supplementation. PON and NO activities were higher in the OVX-ISO+ET group than in the OVX-GD group. In addition, this group had lower caspase-9 and -3 and higher Bcl-2 expression, and there was less aortic apoptotic cell death. These results suggest that a combination of exercise and a soy isoflavone diet has beneficial effects in terms of protecting against cardiovascular risk factors by controlling lipid profiles and the related enzyme, PON, as well as NO activity and apoptosis of the aorta in OVX rats.
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PMID:Combined effects of exercise and soy isoflavone diet on paraoxonase, nitric oxide and aortic apoptosis in ovariectomized rats. 2222 66

Metformin is a biguanide used in the treatment of type 2 diabetes mellitus and obesity. The main mechanism of action is to decrease the intestinal glucose absorption and the hepatic glucose production, however, it does not influence insulin secretion. Metformin also increases the affinity of the insulin receptor, reduces high insulin levels and improves insulin resistance. Additionally, it promotes weight loss. Metformin is a pleiotropic compound but acts, largely, by activating 5 adenosine monophosphate (AMP)-activated protein kinase (AMPK). Data suggest that the therapeutic effects of this compound are mediated, at least in part, through an upregulation of paraoxonase-1 (PON1) synthesis. PON1 is a thiolactonase that degrades lipid peroxides, and downregulates the chemokine (C-C motif) ligand 2 (CCL2) which is a pro-inflammatory chemokine that stimulates the migration of monocytes to areas of inflammation where they differentiate into macrophages. However, the prescription of metformin in patients with liver disease is controversial since, in some cases, this drug causes worsening of liver function. Patients with chronic liver disease have decreased hepatic PON1 activity. A study in mice deficient in PON1 showed that in this experimental model, metformin administration increased the severity of steatosis, increased CCL2 expression, did not activate AMPK, and increased the expression of the apoptosis marker caspase-9. These results suggest that PON1 is essential for the successful activation of AMPK in the liver, and for metformin to demonstrate its therapeutic function.
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PMID:Relationships Between Metformin, Paraoxonase-1 and the Chemokine (C-C Motif) Ligand 2. 2763 39