Disease relevance of Lip1

• We previously reported a rat model of Wolman's disease (Wolman rat) that is deficient for LAL activity [1].
• The aim of the present study was to test whether liver-associated-lymphocytes expressing the NK1.1 marker (NK1.1+ LAL) are substantial for induction of oral tolerance in an experimental colitis model [2].

High impact information on Lip1

• Enzymes included: neutral alpha-glucosidase and lysosomal beta-galactosidase, N-acetyl-beta-glucosaminidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase [3].
• Depletion of NK1.1+ LAL prevented immune tolerance induction in the experimental colitis model [2].
• To evaluate the role of NK1.1+ LAL in keeping the balance between immunogenic and tolerogenic subsets of cells, we tested whether peripheral lymphocytes harvested from tolerized and NK1.1-depleted nontolerized mice can adoptively transfer the tolerance into naive irradiated rats [2].
• These inhibitors, as well as the pH optimum for dolichyl ester hydrolysis, clearly differentiate the enzyme involved from cholesteryl esterase and triglyceride lipase [4].
• Nucleotide sequence analysis showed that Wolman rat LAL cDNA had the same sequence as a RLAL cDNA from the 5'-untranslated region to nt 1101, followed by a 60 bp replacement from nt 1102 to nt 1161 with poly A signal and a 3' 1.8 kb deletion [1].

Chemical compound and disease context of Lip1

• In the laboratory, rats with congenital deficiency of lysosomal acid lipase and marked accumulation of cholesteryl ester, cholesterol free and triglyceride in livers (Wolman's disease rat or Yoshida rat) that corresponded to human Wolman's disease were found and maintained [5].

Biological context of Lip1

• We cloned the RLAL gene from a cDNA library made from normal rat liver mRNA using the human LAL cDNA as a probe, subcloned the RLAL cDNA into pBlueScript vector, and sequenced it [1].
• In this study, we cloned rat LAL (RLAL) cDNA and investigated abnormal LAL gene expression in the Wolman rat [1].
• The deduced amino acid sequence contained 397 amino acids, showed 79.9% homology with human LAL, and had the same functional domains at the same sites as human LAL [1].
• To test the functionality of cholesteryl ester turnover per se, we measured the activities of acyl CoA:cholesterol acyltransferase (ACAT) and cholesteryl esterase, the enzymes involved in cholesteryl ester synthesis and hydrolysis, respectively; we also measured de novo synthesis of cholesterol, cholesteryl esters, and steroids [6].
• These results indicate that the Acid CEH activity varies according to a diurnal rhythm with maxima and minima separated by approximately 12 hr [7].

Anatomical context of Lip1

• The effect of various physicochemical forms of substrate on the activity of acid cholesteryl ester hydrolase isolated from rat liver lysosomes was studied [8].
• Cholesteryl esterase activities were determined in homogenates of rat heart (ventricles), isolated, calcium-tolerant, cardiac myocytes and aortic tissue and were compared with acid and neutral triglyceride lipase activities in these fractions [9].
• An acid cholesteryl ester hydrolase activity associated with a fraction containing mitochondria and lysosomes from rat lactating mammary glands was found to have a pH optimum of 5 [10].
• This change could be accounted for by the decline in activity of neutral cholesteryl esterase in Leydig cells from 18-month-old rats [11].
• Exactly how absorption is inhibited is not clear, but linoleyl tosylate was found to stimulate the activity of cholesteryl esterase prepared from the intestinal mucosa [12].

Associations of Lip1 with chemical compounds

• Pregnant rats, hypophysectomized and hysterectomized on Day 12, were treated for 72 h with either estradiol or testosterone, and luteal microsomal and cytosolic fractions were utilized to measure ACAT and cholesteryl esterase activity, respectively [6].
• Monoglyceride is formed rapidly from diglyceride by a lysosomal acid lipase, although some monoglyceride may be formed directly by phospholipase C hydrolysis of lysophosphatidylcholine [13].
• In contrast, lysosomal acid cholesteryl esterase did not change with age, and acyl CoA: Cholesterol acyltransferase showed only a 33% decrease at 12 months of age [14].
• Hydroxylamine stimulated the inhibition of acid CEH activity by Cu2+ but not that by Zn2+, Fe2+, Co2+, Mn2+, Ca2+, Mg2+ and Hg2+ [15].
• Moreover, addition of chemical radical scavengers to the reaction mixture did not prevent the Cu2+-dependent inhibition of acid CEH activity in the presence of ascorbic acid [15].

Regulatory relationships of Lip1

• Neutral cholesteryl esterase of vascular smooth muscle cells may be regulated by recholesteryl esterase of vascular smooth muscle cells may be regulated by reversible phosphorylation, with the phosphorylated form being the active form [16].

Other interactions of Lip1

• We investigated the effects of insulin, insulin-like growth factor-I (IGF-I), and phorbol 12-myristate 13-acetate (PMA) on neutral cholesteryl esterase activity in cultured rat vascular smooth muscle cells [16].
• It was found that the inhibition of the lysosomal acid lipase activity by rat apolipoprotein A-I (apo A-I) was increased with the degradation of apo A-I by the lysosomal proteases [17].

Analytical, diagnostic and therapeutic context of Lip1

• This animal model could contribute greatly to the clarification of the physiological and pathological roles of lysosomal acid lipase in the metabolism of lipoproteins and cholesterol, and of the pathogenesis of atherosclerosis [18].
• LPS was measured by the QCL-1000 LAL assay, TNFalpha and IFNgamma by ELISA, NO by a colorimetric assay and MDA by the thiobarbiturate assay [19].

References