Abstract
We investigated the possible involvement of Al3+-induced alterations in membrane physical properties in Al3+-mediated inhibition of polyphosphoinositide (PPI) hydrolysis by the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC). Liposomes composed of brain phosphatidylcholine (PC) or of PC and a mixture of brain PPI (PC:PPI) were incubated in the presence of Al3+ (1-100μM). We evaluated: (1) the amount of membrane-bound Al3+, (2) the effects of Al3+ on key membrane physical properties (surface potential, lipid fluidity, and lipid arrangement), and (3) the hydrolysis of PPI. Al3+ binding to PC:PPI (60:40 mol/mol) liposomes was 1.3 times higher than to PC:PPI (90:10 mol/mol) liposomes and did not change after treatment with Triton X-100. Al3+ increased membrane surface potential, promoted the loss of membrane fluidity, and caused lateral phase separation in PC:PPI liposomes. Phosphatidylinositol and phosphatidylinositol monophosphate hydrolysis in the presence of PI-PLC was not affected by Al3+, but a significant and concentration-dependent inhibition of PIP2 hydrolysis was observed, an effect that was prevented by previous bilayer disruption with Triton X-100. The obtained results support the hypothesis that Al3+ binding to liposomes promotes the formation of rigid clusters enriched in PPI, restricting the accessibility of the enzyme to the substrate and subsequently inhibiting PIP2 hydrolysis by PI-PLC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 263-271 |
| Number of pages | 9 |
| Journal | Archives of Biochemistry and Biophysics |
| Volume | 408 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2002 |
| Externally published | Yes |
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Keywords
- Aluminum
- Brain phospholipase C-phosphatidylinositol specific
- Lipid signaling
- Neurotoxicity
- Phosphoinositides
- PIP
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Al3+-mediated changes in membrane physical properties participate in the inhibition of polyphosphoinositide hydrolysis. / Verstraeten, Sandra V.; Oteiza, Patricia I.
In: Archives of Biochemistry and Biophysics, Vol. 408, No. 2, 2002, p. 263-271.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Al3+-mediated changes in membrane physical properties participate in the inhibition of polyphosphoinositide hydrolysis
AU - Verstraeten, Sandra V.
AU - Oteiza, Patricia I.
PY - 2002
Y1 - 2002
N2 - We investigated the possible involvement of Al3+-induced alterations in membrane physical properties in Al3+-mediated inhibition of polyphosphoinositide (PPI) hydrolysis by the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC). Liposomes composed of brain phosphatidylcholine (PC) or of PC and a mixture of brain PPI (PC:PPI) were incubated in the presence of Al3+ (1-100μM). We evaluated: (1) the amount of membrane-bound Al3+, (2) the effects of Al3+ on key membrane physical properties (surface potential, lipid fluidity, and lipid arrangement), and (3) the hydrolysis of PPI. Al3+ binding to PC:PPI (60:40 mol/mol) liposomes was 1.3 times higher than to PC:PPI (90:10 mol/mol) liposomes and did not change after treatment with Triton X-100. Al3+ increased membrane surface potential, promoted the loss of membrane fluidity, and caused lateral phase separation in PC:PPI liposomes. Phosphatidylinositol and phosphatidylinositol monophosphate hydrolysis in the presence of PI-PLC was not affected by Al3+, but a significant and concentration-dependent inhibition of PIP2 hydrolysis was observed, an effect that was prevented by previous bilayer disruption with Triton X-100. The obtained results support the hypothesis that Al3+ binding to liposomes promotes the formation of rigid clusters enriched in PPI, restricting the accessibility of the enzyme to the substrate and subsequently inhibiting PIP2 hydrolysis by PI-PLC.
AB - We investigated the possible involvement of Al3+-induced alterations in membrane physical properties in Al3+-mediated inhibition of polyphosphoinositide (PPI) hydrolysis by the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC). Liposomes composed of brain phosphatidylcholine (PC) or of PC and a mixture of brain PPI (PC:PPI) were incubated in the presence of Al3+ (1-100μM). We evaluated: (1) the amount of membrane-bound Al3+, (2) the effects of Al3+ on key membrane physical properties (surface potential, lipid fluidity, and lipid arrangement), and (3) the hydrolysis of PPI. Al3+ binding to PC:PPI (60:40 mol/mol) liposomes was 1.3 times higher than to PC:PPI (90:10 mol/mol) liposomes and did not change after treatment with Triton X-100. Al3+ increased membrane surface potential, promoted the loss of membrane fluidity, and caused lateral phase separation in PC:PPI liposomes. Phosphatidylinositol and phosphatidylinositol monophosphate hydrolysis in the presence of PI-PLC was not affected by Al3+, but a significant and concentration-dependent inhibition of PIP2 hydrolysis was observed, an effect that was prevented by previous bilayer disruption with Triton X-100. The obtained results support the hypothesis that Al3+ binding to liposomes promotes the formation of rigid clusters enriched in PPI, restricting the accessibility of the enzyme to the substrate and subsequently inhibiting PIP2 hydrolysis by PI-PLC.
KW - Aluminum
KW - Brain phospholipase C-phosphatidylinositol specific
KW - Lipid signaling
KW - Neurotoxicity
KW - Phosphoinositides
KW - PIP
UR - http://www.scopus.com/inward/record.url?scp=0036910812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036910812&partnerID=8YFLogxK
U2 - 10.1016/S0003-9861(02)00557-X
DO - 10.1016/S0003-9861(02)00557-X
M3 - Article
VL - 408
SP - 263
EP - 271
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
IS - 2
ER -