Artikel ; Online: Impact of various buffers and weak bases on lysosomal and intracellular pH
FASEB BioAdvances, Vol 5, Iss 4, Pp 149-
Implications for infectivity of SARS‐CoV‐2
2023 Band 155
Abstract: Abstract Acidification of the cellular lysosome is an important factor in infection of mammalian cells by SARS‐CoV‐2. Therefore, raising the pH of the lysosome would theoretically be beneficial in prevention or treatment of SARS‐CoV‐2 infection. Sodium ... ...
| Abstract | Abstract Acidification of the cellular lysosome is an important factor in infection of mammalian cells by SARS‐CoV‐2. Therefore, raising the pH of the lysosome would theoretically be beneficial in prevention or treatment of SARS‐CoV‐2 infection. Sodium bicarbonate, carbicarb, and THAM are buffers that can be used clinically to provide base to patients. To examine whether these bases could raise lysosomal pH and therefore be a primary or adjunctive treatment of SARS‐CoV‐2 infection, we measured lysosomal and intracellular pH of mammalian cells after exposure to each of these bases. Mammalian HEK293 cells expressing RpH‐LAMP1‐3xFLAG, a ratiometric sensor of lysosomal luminal pH, were first exposed to Hepes which was then switched to sodium bicarbonate, carbicarb, or THAM and lysosomal pH measured. In bicarbonate buffer the mean lysosomal pH was 4.3 ± 0.1 (n = 20); p = NS versus Hepes (n = 20). The mean lysosomal pH in bicarbonate/carbonate was 4.3 ± 0.1 (n = 21) versus Hepes (n = 21), p = NS. In THAM buffer the mean lysosomal pH was 4.7 ± 0.07 (n = 20) versus Hepes (4.6 ± 0.1, n = 20), p = NS. In addition, there was no statistical difference between pHi in bicarbonate, carbicarb or THAM solutions. Using the membrane permeable base NH4Cl (5 mM), lysosomal pH increased significantly to 5.9 ± 0.1 (n = 21) compared to Hepes (4.5 ± 0.07, n = 21); p < 0.0001. Similarly, exposure to 1 mM hydroxychloroquine significantly increased the lysosomal pH to (5.9 ± 0.06, n = 20) versus Hepes (4.3 ± 0.1, n = 20), p < 0.0001. Separately steady‐state pHi was measured in HEK293 cells bathed in various buffers. In bicarbonate pHi was 7.29 ± 0.02 (n = 12) versus Hepes (7.45 ± 0.03, [n = 12]), p < 0.001. In cells bathed in carbicarb pHi was 7.27 ± 0.02 (n = 5) versus Hepes (7.43 ± 0.04, [n = 5]), p < 0.01. Cells bathed in THAM had a pHi of 7.25 ± 0.03 (n = 12) versus Hepes (7.44 ± 0.03 [n = 12]), p < 0.001. In addition, there was no statistical difference in pHi in bicarbonate, carbicarb or THAM solutions. The results of ... |
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| Schlagwörter | alkalinization ; carbicarb ; lysosomal pH ; sars‐Covid‐ 19 ; sodium bicarbonate ; tham ; Biology (General) ; QH301-705.5 |
| Thema/Rubrik (Code) | 572 |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-04-01T00:00:00Z |
| Verlag | Wiley |
| Dokumenttyp | Artikel ; Online |
| Datenquelle | BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl) |
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