PAWLIK MONOCYTES AND VASCULAR ENDOTHELIAL CELLS APOPTOSIS . ROLE OF P-HSP 27

Apoptosis is a genetically programmed cell death occurring during both the physiological phenomena such as organogenesis, and pathological conditions including atherosclerosis. Apoptotic death is characterized by nuclear fragmentation, cell shrinkage, loss of membrane asymmetry, chromatin condensation and chromosomal deoxyribonucleic acid (DNA) fragmentation. This process is adenosine triphosphate (ATP) dependent (1). So far two major apoptotic pathways were described: extrinsic and intrinsic. The former is caused by joining of ligand to death receptors: Tumor necrosis factor receptor-1 (TNFR1), Fas, death receptors 3 to 6 (DR3-6) and subsequent activation of caspases 8 or 10, and in consequence – executioner caspases 3, 6 and 7. Substrates for these executioners include Poli-(ADP ribose) polymerase (PARP), lamine, fodrin, gelsolin and DFF. The latter is activated when, for example, DNA damage, oxidative stress appear. The apoptosom consisting of cytochrome c, Apaf-1 and procaspase 9 is the place where caspase 9 activation occurs. The downstream events are the same as in extrinsic pathway (2). Crucial role in determining whether to switch to apoptosis or not, depends on proteins family Bcl-2. It includes antiapoptotic Bcl-2, Bcl-XL, proapoptotic Bax, Bak and proapoptotic Bid, p53 up-regulated modulator of apoptosis (PUMA) that are superior to the rest of Bcl-2 family. However, apoptosis phenomenon independent of caspases also may take place. Apoptosis inducing factor (AIF) and Endo G also trigger apoptotic death by mechanism which is still poorly understood (3, 4). Heat shock proteins (HSPs) are divided into various families according to their size: small HSPs, HSP70, HSP90 and HSP110. HSPs are the ubiquitous in cells and one of their main functions is maintenance of cellular homeostasis. In recent years many studies have been made to investigate their effect on the regulation of apoptosis. In particular HSP27 and HSP70 are known to have special antiapoptotic properties (5). HSP70 may prevent cells from the apoptotic death induced by common lethal factors as TNF-α, or growth factors withdrawal on the different stages of apoptotic cascade. HSP70 may be involved in APAF-1 binding, apoptosis inducing factor (AIF) binding, c-Jun Nterminal Kinase (JNK) inhibition, prevention of morphological changes induced by caspase 3 and interactions with p53 and cmyc (6). HSP27, in turn, binds procaspase 3, prevents apoptosom formation due to interactions with cytochrome c, binds to Daxx protein and interacts with cytoprotective protein kinase B (PKB/Akt) (7). Physiological stimuli as well as various forms of stress trigger phosphorylation of HSP27. Phosphorylated form of HSP27 (p-HSP27) is translocated to nucleus, where performs functions necessary for cell survival (8). Vascular endothelium is under permanent exposure to many factors which may activate death or survival pathways in the vascular cells. Cells answer to stimuli depends on predominance of proor antiapoptotic signals the cells receive. Vascular JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2009, 60, 4, 55-61 www.jpp. krakow.pl