The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue

Ali, Aus Tariq; Penny, Clem; Paiker, Janice; Psaras, George K.; Ikram, Faisel; Crowther, Nigel J.

doi:10.1258/000456306776865179

Cited by 39 publications

(39 citation statements)

References 40 publications

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“…9,10 The present study has confirmed the parallel relationship between elevated ALP enzyme activity and cellular fat accumulation in abdominal subcutaneous adipose tissue. The intracellular deposition of lipid is the defining feature of the maturation of preadipocytes into adipocytes, a process termed "adipogenesis".…”

Section: Discussionsupporting

confidence: 84%

“…22 It should be noted that levamisole inhibits ALP activity in cell extracts of human preadipocytes. 10 This confirms that it is the tissue-non-specific form. Thus, levamisole only activates ALP activity in human preadipocytes with intact membranes, 10 suggesting that this process is modulated by factors residing in the cell membrane system, the identities of which are currently unknown.…”

Section: Discussionsupporting

confidence: 60%

“…Results from 3T3-L1 cells using ALP inhibitors and PCR demonstrate that it is the tissue-non-specific isoform that is expressed in this cell type. 9 The ability of levamisole to increase ALP activity in human preadipocytes has been reported previously, 10 and a study of rat hepatocytes, which are known to express the tissue-non-specific ALP isoform, also showed a similar effect. 22 It should be noted that levamisole inhibits ALP activity in cell extracts of human preadipocytes.…”

Section: Discussionsupporting

confidence: 52%

“…8 Previously, we demonstrated a positive correlation between ALP activity and fat accumulation in murine 3T3-L1 preadipocytic cells 9 and human mammary gland preadipocytes. 10 The ability of ALP inhibitors to pharmacologically inhibit intracellular lipid accumulation suggests that ALP may play a role in preadipocyte lipid storage. 9,10 It is not known whether ALP is expressed in other body fat depots, or whether it is involved in the molecular control of adipogenesis at such sites.…”

Section: Introductionmentioning

confidence: 99%

“…10 The ability of ALP inhibitors to pharmacologically inhibit intracellular lipid accumulation suggests that ALP may play a role in preadipocyte lipid storage. 9,10 It is not known whether ALP is expressed in other body fat depots, or whether it is involved in the molecular control of adipogenesis at such sites. Abdominal subcutaneous adipose tissue is an important fat storage depot and may influence whole body insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Ali

Ferris

Penny

et al. 2013

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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Background: Alkaline phosphatase (ALP) controls intracellular lipid accumulation in human preadipocytes, but it is not known whether ALP is expressed in all body fat depots, or whether it has a similar role at all sites.Design: Cross-sectional.Setting and subjects: Subjects undergoing breast reduction and abdominal fat biopsies operations at Charlotte Maxeke Johannesburg Academic Hospital. Outcome measures:This study compared intracellular lipid accumulation and ALP activity in the presence and absence of ALP inhibitors in preadipocytes that were obtained from different adipose depots. Abdominal and mammary gland preadipocytes were isolated from women and induced to differentiate in culture. ALP activity and intracellular lipid levels were measured at baseline and after 12 days of differentiation in the presence and absence of the ALP inhibitors, histidine and levamisole.Results: ALP activity was detected in nondifferentiated abdominal (134 ± 7.5 mU/mg protein) and mammary gland (136 ± 9.6 mU/mg protein) preadipocytes. Its activity had increased significantly (p-value < 0.0005 for both) by day 12 of differentiation (388 ± 55 for abdominal and 278 ± 28 mU/mg protein for mammary). Preadipocytes treated with histidine had lower fat accumulation (p-value < 0.0005) and ALP activity (p-value < 0.005) than nontreated cells on day 12, while those treated with levamisole had lower fat accumulation (p-value < 0.005), but elevated ALP activity (p-value < 0.05), compared to nontreated cells. Lipid accumulation (p-value < 0.005) and ALP activity (p-value < 0.05) were higher in abdominal than mammary gland preadipocytes by day 12.Conclusion: ALP is involved in the control of intracellular lipid accumulation in human preadipocytes that are isolated from both adipose depots. The ability of levamisole to inhibit this process while activating ALP, suggests that this molecule acts via an ALP-independent pathway, while histidine attenuates both lipid deposition and ALP activity.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Ali

Ferris

Penny

et al. 2013

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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Recent advances with alkaline phosphatase isoenzymes and their inhibitors

Zaher

El‐Gamal

Omar

et al. 2020

Archiv der Pharmazie

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Alkaline phosphatases are found in different living species and play crucial roles in various significant functions, such as hydrolyzing a variable spectrum of phosphatecontaining physiological compounds, contributing to DNA synthesis, bone calcification, and attenuation of inflammation. They are homodimeric enzymes; each subunit contains one magnesium ion and two zinc ions crucial for the catalytic activity of the enzyme. Alkaline phosphatases exist in four distinct isoenzymes (placental, intestinal, germ cell, and tissue nonspecific alkaline phosphatases), which are expressed by four different genes; each one of them has distinguished functions. Any disturbance in the gene expression of alkaline phosphatase eventually induces serious disease conditions. Thus, the need to explore new lead inhibitors has increased recently. In this literature review, we aim to investigate the role of alkaline phosphatase in different diseases and physiological conditions and to study the structure-activity relationships of recently reported inhibitors. We focused on the lead compounds reported in the last 5 years (between 2015 and 2019). K E Y W O R D S alkaline phosphatase, inhibitors, isoenzymes, structure-activity relationship

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Synthesis of 2‐(1H‐Benzo[d]imidazol‐2‐yl)phenyl Phosphate as a Fluorescent Probe for Determination of ALP

Lei¹,

Ouyang²,

Zhang

et al. 2009

Chin. J. Chem.

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A convenient method to synthesize 2-(1H-benzo [d]imidazol-2-yl)phenyl phosphate (HBIPP), a substrate for the fluorescent determination of alkaline phosphatase (ALP) activity, via the reaction of salicylaldehyde and o-phenylenediamine in the presence of manganese(III) acetate was realized. The structure was confirmed by IR, 1 H NMR, EI-MS and elemental analysis studies while the corresponding photo-physical properties of the enzyme reaction product were characterized by ultraviolet absorption and fluorescence spectra in methanol. Preliminary tests reveal that the amount of the enzyme reaction product, 2-(2-hydroxyphenyl) benzimidazole (HPBI), is proportional to ALP activity in the range of 0.01-5 U/L with the detection limit of 8.5 mU/L, which can be applied to assess ALP in biomedical research.

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The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue

Abstract: Addresses

Cited by 39 publications

References 40 publications

Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Recent advances with alkaline phosphatase isoenzymes and their inhibitors

Synthesis of 2‐(1H‐Benzo[d]imidazol‐2‐yl)phenyl Phosphate as a Fluorescent Probe for Determination of ALP

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