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Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

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Related in: MedlinePlus

Some typical lipid mediators capable of altering the Hsp response. The parental molecules of a variety of lipid mediators (boxes) are:(1) glycerolipids of the bulk membrane; constituents of rafts such as (2) SM and (3) cholesterol. PLA2: phospholipase A2; SMase: sphingomyelinase; SGT: sterol glucosyltransferase; COX: cyclooxygenase and LOX: lipoxygenase.
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fig07: Some typical lipid mediators capable of altering the Hsp response. The parental molecules of a variety of lipid mediators (boxes) are:(1) glycerolipids of the bulk membrane; constituents of rafts such as (2) SM and (3) cholesterol. PLA2: phospholipase A2; SMase: sphingomyelinase; SGT: sterol glucosyltransferase; COX: cyclooxygenase and LOX: lipoxygenase.

Mentions: Many of the lipid mediators (e.g. leukotrienes, prostaglandins and certain lysophospholipids) leave the host cells and bind to GPCRs in the surface membrane of the same or neighbouring cells. Other lipid signals converge on PLC, PIs or Ca2+. As highlighted in Fig. 7 the typical non-raft phospholipids and raft lipid classes (i.e. cholesterol and SM) can equally serve as stress-response modulating factors. Phospholipids are reservoirs of arachidonic acid. Phospholipase A2 is known to be activated by different stressors, and the concomitant release of arachidonic acid can stimulate heat shock factor1 (HSF1)-DNA binding, increase the phosphorylation of HSF1 and ultimately up-regulate some Hsps [288]. On the other hand, arachidonic acid is used in the synthesis of prostaglandins via cyclooxygenases, some of which are also potent Hsp inducers ([289] and see references in [16, 287]). Moreover, certain lipoxygenase products of arachidonic acid, such as 12-hydroxyeicosatetraenoic acid, have also been shown to induce the expression of individual Hsps inhuman leucocytes [290]. Upon exposure to environmental stress, cholesterol can rapidly transform to cholesteryl glucoside, and its production is followed by the activation of certain protein kinases also engaged in the induction of Hsps [291]. Similar to cholesterol, SM may play both structural and functional roles as a raft lipid, and in parallel it takes part in the generation and transduction of Hsp signals. Within the large SM family of lipid mediators, the reactions are reversible and the lipids are intercon-vertible. Ceramide and sphingosine can be released by the sequential cleavage of SM under various stress conditions [292]. Ceramide, ceramide-1-phosphate, sphingosine and sphingosine-1-phosphate have all been shown to carry out second messenger functions linked ultimately to refinement of the cellular Hsp pattern [293].


Membranes: a meeting point for lipids, proteins and therapies.

Escribá PV, González-Ros JM, Goñi FM, Kinnunen PK, Vigh L, Sánchez-Magraner L, Fernández AM, Busquets X, Horváth I, Barceló-Coblijn G - J. Cell. Mol. Med. (2008)

Some typical lipid mediators capable of altering the Hsp response. The parental molecules of a variety of lipid mediators (boxes) are:(1) glycerolipids of the bulk membrane; constituents of rafts such as (2) SM and (3) cholesterol. PLA2: phospholipase A2; SMase: sphingomyelinase; SGT: sterol glucosyltransferase; COX: cyclooxygenase and LOX: lipoxygenase.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401130&req=5

fig07: Some typical lipid mediators capable of altering the Hsp response. The parental molecules of a variety of lipid mediators (boxes) are:(1) glycerolipids of the bulk membrane; constituents of rafts such as (2) SM and (3) cholesterol. PLA2: phospholipase A2; SMase: sphingomyelinase; SGT: sterol glucosyltransferase; COX: cyclooxygenase and LOX: lipoxygenase.
Mentions: Many of the lipid mediators (e.g. leukotrienes, prostaglandins and certain lysophospholipids) leave the host cells and bind to GPCRs in the surface membrane of the same or neighbouring cells. Other lipid signals converge on PLC, PIs or Ca2+. As highlighted in Fig. 7 the typical non-raft phospholipids and raft lipid classes (i.e. cholesterol and SM) can equally serve as stress-response modulating factors. Phospholipids are reservoirs of arachidonic acid. Phospholipase A2 is known to be activated by different stressors, and the concomitant release of arachidonic acid can stimulate heat shock factor1 (HSF1)-DNA binding, increase the phosphorylation of HSF1 and ultimately up-regulate some Hsps [288]. On the other hand, arachidonic acid is used in the synthesis of prostaglandins via cyclooxygenases, some of which are also potent Hsp inducers ([289] and see references in [16, 287]). Moreover, certain lipoxygenase products of arachidonic acid, such as 12-hydroxyeicosatetraenoic acid, have also been shown to induce the expression of individual Hsps inhuman leucocytes [290]. Upon exposure to environmental stress, cholesterol can rapidly transform to cholesteryl glucoside, and its production is followed by the activation of certain protein kinases also engaged in the induction of Hsps [291]. Similar to cholesterol, SM may play both structural and functional roles as a raft lipid, and in parallel it takes part in the generation and transduction of Hsp signals. Within the large SM family of lipid mediators, the reactions are reversible and the lipids are intercon-vertible. Ceramide and sphingosine can be released by the sequential cleavage of SM under various stress conditions [292]. Ceramide, ceramide-1-phosphate, sphingosine and sphingosine-1-phosphate have all been shown to carry out second messenger functions linked ultimately to refinement of the cellular Hsp pattern [293].

Bottom Line: Moreover, their alteration has been associated with the development of numerous diseases.The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs.In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Cell Biomedicine, Dept of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain. pablo.escriba@uib.es

ABSTRACT
Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

Show MeSH
Related in: MedlinePlus