Biochemical evidence for Ca2+-independent functional activation of hPLSCR1 at low pH
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Vincent Gerard Francis
Abstract
Human phospholipid scramblase 1 (hPLSCR1) is a Ca2+-dependent protein known to scramble phospholipids in the plasma membrane resulting in loss of membrane asymmetry. It has been reported that hPLSCR1 exhibits Ca2+- independent activity at low pH. However, the conformational changes induced at low pH leading to functional activation are not known. Our results showed that recombinant hPLSCR1 was functionally activated at low pH, which is similar to the behavior of natively extracted hPLSCR1. Tryptophan fluorescence measurements showed a decrease in Ca2+-binding affinity at low pH, although not at pH 5.5. Far and near UV-CD revealed that low pH induced structural changes, with a significant increase in the β-sheet content of the protein. At the physiological level, decreased hPLSCR1 expression was observed after a period of exposure to low pH. The effect occurred at the promoter level. The expression levels of hPLSCR1 directly correlated with the sensitivity of HEK293 to apoptosis. Based on these results, we conclude that the mechanisms of Ca2+- and pH-induced functional activation of hPLSCR1 are different and that hPLSCR1 expression regulated by low pH could provide insights into the role of hPLSCR1 in cancer progression.
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© University of Wrocław, Poland
Artikel in diesem Heft
- Biochemical evidence for Ca2+-independent functional activation of hPLSCR1 at low pH
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Artikel in diesem Heft
- Biochemical evidence for Ca2+-independent functional activation of hPLSCR1 at low pH
- Catabolism of chondroitin sulfate
- The effect of hypoxia on PGE2-stimulated cAMP generation in HMEC-1
- Is there a connection between inflammation, telomerase activity and the transcriptional status of telomerase reverse transcriptase in renal failure?
- The beta-actin gene promoter of rohu carp (Labeo rohita) drives reporter gene expressions in transgenic rohu and various cell lines, including spermatogonial stem cells
- Molecular machines – a new dimension of biological sciences
- Therapeutic potential of PACAP for neurodegenerative diseases
- A newly isolated yeast as an expression host for recombinant lipase
- Identification of shorter length lamin A protein in mouse ear cartilage tissue
- Relationship among IL-6, LDL cholesterol and lipid peroxidation
- Study strategies for long non-coding RNAs and their roles in regulating gene expression
