Biomaterial Database

Impairment of the sarcolemmal phospholipase D-phosphatidate phosphohydrolase pathway in diabetic cardiomyopathy. 1998

S A Williams, and P S Tappia, and C H Yu, and M Bibeau, and V Panagia

Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Winnipeg, Canada.

Experimental evidence suggests that the myocardial phospholipase D (PLD)-phosphatidate phosphohydrolase (PAP) signalling pathway may regulate Ca2+ movements and contractile performance of the heart. As abnormal Ca2+ homeostasis is associated with diabetic cardiomyopathy, we examined the functional status of the PLD/PAP pathway in sarcolemmal (SL) membranes isolated from insulin-dependent diabetic rat hearts at 8 weeks after a single i.v. injection of streptozotocin (65 mh/kg b.w.). Compared to age-matched controls, SL PLD hydrolytic (producing phosphatidic acid, PtdOH) and transphosphatidylation activities were significantly depressed in diabetic animals, while SL PAP was significantly augmented. The net effect of the altered enzyme activities in diabetic animals was a severely diminished (by 67% of controls) membrane level of PLD-derived PtdOH. Two weeks of insulin therapy to the 6 week diabetic animals normalized PLD, while PAP activity and PtdOH level were significantly modified, but had not completely reverted to control values. The observed changes were not due to hypothyroidism associated to the diabetic model as the induction of hypothyroidism in healthy non-diabetic animals did not affect SL PLD and PAP. The results suggest that the severe reduction of PLD-derived PtdOH and increased production of sn-1,2-diacylglycerol by phosphatidate phosphohydrolase may lead to an impairment of the bioprocesses mediated by these signalling lipids.

UI	MeSH Term	Description	Entries
D007037	Hypothyroidism	A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.	Central Hypothyroidism,Primary Hypothyroidism,Secondary Hypothyroidism,TSH Deficiency,Thyroid-Stimulating Hormone Deficiency,Central Hypothyroidisms,Deficiency, TSH,Deficiency, Thyroid-Stimulating Hormone,Hormone Deficiency, Thyroid-Stimulating,Hypothyroidism, Central,Hypothyroidism, Primary,Hypothyroidism, Secondary,Hypothyroidisms,Primary Hypothyroidisms,Secondary Hypothyroidisms,TSH Deficiencies,Thyroid Stimulating Hormone Deficiency,Thyroid-Stimulating Hormone Deficiencies
D007328	Insulin	A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).	Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297	Male		Males
D009202	Cardiomyopathies	A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).	Myocardial Disease,Myocardial Diseases,Myocardial Diseases, Primary,Myocardial Diseases, Secondary,Myocardiopathies,Primary Myocardial Disease,Cardiomyopathies, Primary,Cardiomyopathies, Secondary,Primary Myocardial Diseases,Secondary Myocardial Diseases,Cardiomyopathy,Cardiomyopathy, Primary,Cardiomyopathy, Secondary,Disease, Myocardial,Disease, Primary Myocardial,Disease, Secondary Myocardial,Diseases, Myocardial,Diseases, Primary Myocardial,Diseases, Secondary Myocardial,Myocardial Disease, Primary,Myocardial Disease, Secondary,Myocardiopathy,Primary Cardiomyopathies,Primary Cardiomyopathy,Secondary Cardiomyopathies,Secondary Cardiomyopathy,Secondary Myocardial Disease
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010711	Phosphatidate Phosphatase	A phosphomonoesterase involved in the synthesis of triacylglycerols. It catalyzes the hydrolysis of phosphatidates with the formation of diacylglycerols and orthophosphate. EC 3.1.3.4.	Phosphatidate Phosphohydrolase,Phosphatidic Acid Phosphatase,Phosphatidic Acid Phosphohydrolase,Phosphatase, Phosphatidate,Phosphatase, Phosphatidic Acid,Phosphohydrolase, Phosphatidate,Phosphohydrolase, Phosphatidic Acid
D010739	Phospholipase D	An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.	Lecithinase D,Phosphatidylcholine Phosphohydrolase
D003921	Diabetes Mellitus, Experimental	Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.	Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004075	Diglycerides	Glycerides composed of two fatty acids esterified to the trihydric alcohol GLYCEROL. There are two possible forms that exist: 1,2-diacylglycerols and 1,3-diacylglycerols.	Diacylglycerol,Diacylglycerols
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme