• 圣淘沙名胜世界(新加坡)

    An optimised protocol for the detection of lipofuscin in cells cultured in vitro

    Camilla SA Davan-Wetton, Trinidad Montero-Melendez

    Published: 2024-06-18 DOI: 10.17504/protocols.io.x54v9yw91g3e/v1
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    Abstract

    Lipofuscin is a complex material that accumulates in lysosomes and it is considered a marker of cellular senescence and ageing. This substance can be detected using the lipophilic stain Sudan Black B. This protocol describes an easy, straightforward and inexpensive method for the staining of lipofuscin using Sudan Black B and imaging via brightfield microscopy. Additionally, this protocol offers an alternative method for detection of Sudan Black B stained lipofuscin using fluorescence microscopy, which facilitates co-staining of Sudan Black B with conventional antibody-based immunofluorescence staining techniques.

    Before start

    This protocol is optimised for the staining of cells cultured in vitro in 24-well plates. Plate your cells and treat with appropriate compounds or stimuli for the required time. Remember to prepare the Saturated Sudan black B solution (steps 1-2) the day before you plan to stain your cells, as this solution requires to be stirred overnight for complete dissolution.

    Steps

    Saturated Sudan Black B solution preparation

    1.

    Dissolve 1.2g Sudan Black B in 80mL 70% ethanol in a glass bottle and stir on a magnetic stirrer.

    2.

    Before use, filter the solution three times as follows:

    - first through a  **70μm**  cell strainer
    
    
    
    - then through a  **0.45μm**  syringe filter
    
    
    
    - finally through a  **0.22μm**  syringe filter.
    

    Note
    Prepare Sudan Black solution fresh. Storing and re-using old solutions is not recommended.

    Nuclear Fast Red solution preparation

    3.

    Prepare a 5% aluminium sulphate solution by dissolving 25g aluminium sulphate in 500mL of distilled water. Stir until dissolved, sterilise by filtration using a 0.22μm filter and store at Room temperature .

    Note
    Sterilisation is recommended when preparing a larger volume of aluminium sulphate to prevent microorganism growth, as a 500ml batch can last for several months.

    4.

    Dissolve 200mg Nuclear Fast Red in 200mL boiling 5% aluminium sulphate solution. Boil for 0h 5m 0s and allow it to return to Room temperature before use.

    Sudan Black B staining

    5.

    Remove cell culture medium and wash cells once in PBS.

    Note
    For this and subsequenct steps where solutions are removed, an aspirator with a trap flask can be used.

    6.

    Fix cells in 4% PFA for 0h 15m 0s at Room temperature.

    Note
    PFA is a chemical hazard and needs to be used inside a chemical fume hood.

    7.

    Remove PFA solution and incubate cells in 70% ethanol for 0h 2m 0s .

    Note
    PFA is a chemical hazard and needs to be disposed of in an appropriate waste container.

    8.

    iunspecificRemove ethanol and incubate cells in the freshly prepared, triple filtered Sudan Black B solution for 0h 8m 0s. Place plate on a plate shaker at 200rpm for the duration of the staining.

    Note
    Shaking the plate during the staining process is strongly advised to avoid SBB precipitates which will produce unspecific staining.

    9.

    Remove Sudan Black B solution and wash the cells in distilled water for 0h 5m 0s, replacing the plate on the plate shaker at 200rpm for the duration of the washing.

    Note
    Sudan Black B solution should be disposed of according to local waste management regulations and should not enter the drainage system. At this stage, the protocol is subdivided depending if qualitative (A) or quantitative (B) staining is desired.

    A) Counterstaining with Nuclear Fast Red solution

    10.

    Remove the distilled water and incubate cells in the Nuclear Fast Red solution for 0h 10m 0s. Place the plate on the plate shaker at 200rpm for the duration of the staining.

    11.

    Remove the Nuclear Fast Red solution and wash wells in PBS for 0h 10m 0s, replacing the plate on the plate shaker at 200rpm for the duration of the washing.

    12.

    Replace the PBS with fresh PBS and visualise cells using a brightfield microscope.

    B) Quantification of Sudan Black B staining

    13.

    Remove the distilled water and incubate cells in 1ug/ml DAPI solution for 0h 10m 0s .

    Note
    The plate should be protected from light by covering with aluminium foil from now onwards as DAPI is light sensitive.

    14.

    Remove the DAPI solution and wash the cells once in PBS for 0h 10m 0s, replacing the plate on the plate shaker at 200rpm for the duration of the washing.

    15.

    Replace the PBS with fresh PBS and visualise cells using a fluorescence microscope. Sudan Black B can be visualised with a Cy5 filter (far-red, 628/40 nm Excitation; 692/40 nm Emission).

    16.

    Quantification may be performed, either by calculating the proportion of fluorescent cells (i.e. percentage of positive cells), or by measuring the total fluorescence intensity per cell.

    Note
    Total fluorescence can be quantified in Fiji using the 'Integrated Density' measurement.

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