Disease relevance of PDLIM3

• Exclusion of muscle specific actinin-associated LIM protein (ALP) gene from 4q35 facioscapulohumeral muscular dystrophy (FSHD) candidate genes [1].
• The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a predominance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reductions in high density lipoprotein, and a 3-fold increased risk of myocardial infarction [2].
• METHODS: Patients with knee arthritis (not due to gout, osteoarthritis, or septic arthritis) were randomized over 3 treatment arms: ALC, ALP, and JAC [3].
• Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30% [4].
• The study assessed the efficacy of fish oil supplementation in counteracting the classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP) [5].

High impact information on PDLIM3

• This result suggests the possibility that genetic variation at the LDL receptor locus or a closely linked locus on chromosome 19 may be responsible for metabolic alterations in ALP pattern B that account for a substantial proportion of the familial predisposition to coronary artery disease in the general population [2].
• The maximum logarithm of odds (LOD) score of 4.07 was observed at a recombination fraction of 0.04, assuming 100% penetrance of ALP pattern B, and 4.27 at a recombination fraction of zero, assuming 90% penetrance of pattern B [2].
• Results: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point [6].
• Here, we used mutagenesis, kinetic analysis, and computer modeling to identify the residues important for the binding of known ALP inhibitors to the TNALP active site [7].
• MATERIALS AND METHODS: We measured biochemical markers of bone turnover (bone-specific alkaline phosphatase [bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo [4].

Chemical compound and disease context of PDLIM3

• As expected, the decrease of both bone formation markers (bone ALP and PINP) was delayed compared to that of bone resorption and significant (p < 0.05-0.01) only after 2 months of treatment in the estrogen-treated group compared to the placebo group [8].
• RESULTS: We noted normal bilirubin, AST, ALT, and ALP levels in 14.5%, 12.3%, 11.2%, and 26.4% of cases of acute biliary pancreatitis respectively [9].
• The other ALP isozyme of FL cells had properties common to hepatoma ALP with regard to L-phenylalanine sensitivity, inhibition by ethylenediaminetetraacetate, inactivation by urea, and antigen site, but differed from it in electrophoretic mobility, sensitivity to L-leucine and L-homoarginine, and the presence of another antigen site [10].
• As bone resorption markers, urinary free and total deoxypyridinoline as well as urinary collagen type I C-terminal telopeptide were measured; as bone formation markers, serum bone type and total alkaline phosphatase (BALP and ALP) levels along with osteocalcin (OC) were used [11].
• The ALP (alkyl-lysophospholipid) edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine; Et-18-OCH3) induces apoptosis in S49 mouse lymphoma cells [12].

Biological context of PDLIM3

• Although this strong SMF exposure did not affect cell proliferation, it up-regulated cell differentiation and matrix synthesis as determined by ALP and alizarin red stainings, respectively [13].
• Our data demonstrate the efficacy of fish oil fatty acids in counteracting the proatherogenic lipid profile of the ALP but also that the apoE genotype influences responsiveness to this dietary treatment [5].
• We conclude that the favorable influence of dietary n-3 PUFA on the ALP may be mediated, in part, through an increase in the plasma activity and gene expression of lipoprotein lipase in human adipose tissue [14].
• Serum bone-specific alkaline phosphatase (S-bone ALP) and serum osteocalcin (S-OC) were assessed as markers of bone formation [15].
• Lack of association between lipaemia and central adiposity in subjects with an atherogenic lipoprotein phenotype (ALP) [16].

Anatomical context of PDLIM3

• Interestingly, this group included genes that encode actin filament binding and regulatory proteins, such as gelsolin, PDZ and LIM domain 3 (PDLIM3) and troponin I1 [17].
• ALP activity was synergistically increased by the treatment with a specific MEK-1 inhibitor PD98059 and rhBMP-2 in both cell lines [18].
• When administered at intermediate stages of osteoblast differentiation (days 12, 15 and 18) BSP remained refractory to rhOP-1 whereas the ALP was increased almost 2-fold, independent of the constitutive levels of mRNA expression [19].
• Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 mug/L; ICTP: 5.6 vs 3.3 mug/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 mug/L, and 3.5 vs 3.2 mug/L, respectively, in the malleolar fracture group) [20].
• RESULTS: In intact articular cartilage, ALP accumulated to a significantly higher degree than myoglobin [21].

Associations of PDLIM3 with chemical compounds

• A type I collagen synthesis inhibitor L-azetidine-2-carboxylic acid, as well as osteocalcin (OCN), significantly antagonized Smad3-stimulated ALP activity and mineralization of MC3T3-E1 cells [22].
• However, in our PCOS patients, because of relatively low triglyceride levels, complete ALP is uncommon [23].
• The change in ALP and bilirubin observed from the precholangiographic value up to 2 and 12 months afterward was not significantly different in those with and without DS [24].
• The objective of this study was to determine whether a predominance of small, dense LDL (LDL-III, d = 1.044-1.063 g/ml) in the circulation in association with an atherogenic lipoprotein phenotype (ALP) (i.e. LDL-III > 100 mg/dl, an elevated plasma triglyceride and a low high density lipoprotein cholesterol) alters LDL reactivity towards APG [25].
• Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues [26].

Analytical, diagnostic and therapeutic context of PDLIM3

• OBJECTIVE: To compare the efficacy of arthroscopic lavage plus administration of corticosteroids (ALC), arthroscopic lavage plus administration of placebo (ALP), and joint aspiration plus administration of corticosteroids (JAC) in knee arthritis, and to evaluate whether clinical or histologic characteristics determine outcome [3].
• ALP scintigraphy may represent a functional assay for early, premorphological cartilage alterations in human arthritis as well [21].
• In a randomized, double blind, placebo-controlled, cross-over study, 51 male subjects expressing an atherogenic lipoprotein phenotype (ALP) had their diets supplemented with fish oil for 6 weeks [14].
• A dietary intervention study was undertaken to examine the effects of an ALA-enriched diet in 57 men expressing an atherogenic lipoprotein phenotype (ALP) [27].
• The DNA analysis revealed that the cells of the control group and the HOP-26 positive cells showed a 5 times higher cell growth compared to the STRO-1 and ALP positive cells [28].

References