كليدواژه :
Peroxisome , Peroxisome proliferation , Genetic disorders , Stem Cells
چكيده فارسي :
Eukaryotic cells are compartmentalized into functionally distinct organelles,
consisting distinct proteins with specialized functions. Peroxisomes, single membrane
surrounded spherical organelles, are the sites of various metabolic pathways in the
most of higher organisms including human which is fundamental to life. peroxisomes
perform a range of various functions like oxidation of very long chain fatty acids,
generation and removal of hydrogen peroxide, while peroxisomes have also been
implicated in β-oxidation of aromatic and cyclic compounds, synthesis of
plasmalogens, isoprenoids, lysine and glycine betaine, metabolism of purines and
pyrimidines, and catabolism of polyamines, D-amino acids and methanol. Moreover
peroxisomes are participated in signaling and developmental pathways. Disruption of
those functions in human leads to severe disorders, mainly cause death several weeks
after the birth. The peroxisomal disorders (PDs) are usually subdivided into two
groups, including: (i) the peroxisome biogenesis disorders (PBDs); and (ii) the single
peroxisomal enzyme (transporter) deficiencies (PEDs). The PBD group comprises
Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD); infantile Refsum
disease (IRD) and rhizomelic chondrodysplasia punctata (RCDP) type 1. Peroxisome
biogenesis disorders (PBDs) are caused by defects in import of peroxisome matrix
proteins and biosynthesis of peroxisomal membrane proteins. Thus the proper
function of peroxisome needs a well performance of a series of events that result in
correct biogenesis and assembly of peroxisome. Using of various experimental model
systems including yeast and Chinese hamster ovary (CHO) cell mutants, large number
of genes have been identified which are responsible for peroxisome biogenesis termed
PEX genes which encoded functional proteins (Pex) required for the event of
peroxisome formation in the cells. Thirty two PEX genes have so far been identified.
All peroxisomal proteins are encoded by nuclear genes, synthesized on free
polysomes, and post translationally imported into pre-existing peroxisomes. The
majority of matrix proteins contain either of two peroxisome targeting signal (PTS),
PTS1 or PTS2. Proteins with these signals are recognized and trapped by specific
cytosolic receptors, Pex5p and Pex7p. Despite to unraveling mechanisms of
peroxisomal targeting of matrix proteins, much less is known regarding to the
targeting and assembly of peroxisomal membrane proteins (PMPs). They do not
contain a recognizable PTS1 or PTS2 sequence. Thus, their targeting, are PTS1 and
PTS2 independent manner. Here we are intend to introduce a brief description of
those genes and the characteristics of their corresponded proteins and related
peroxisomal biogenesis disorders with a brief explanation for the diagnosis techniques
which are applied for proper detection.
Moreover, the proliferations of the peroxisomes are under regulation of several
transcription factors termed Peroxisome proliferator activated receptors (PPARs).
PPARs are ligand activated transcription factors that belong to the nuclear hormone
receptor superfamily. PPAR target genes encode enzymes involved not only in
peroxisomal and beta-oxidation, and production of fatty acid binding proteins, but
also exert different functions in a wide range of tissues including differentiation,
proliferation especially in processes of neural and adipose cells differentiation. PPARs
function as sensors for both endogenous and exogenous stimuli and this sensing
mechanism regulates lipid homeostasis. Three isoforms of PPAR, designated α, γ, β/δ,
have been identified so far which, are encoded by separate genes. PPARs possess a
highly conserved DNA binding domain, with two zinc fingers, that recognizes
peroxisome proliferator response elements (PPREs) in the promoter regions of target
genes. They also contain two transcriptional activation function (AF) domains, in the
ligand binding domain. Their molecular structures and diverse functions will be
presented.
Keywordes: Peroxisome, Proliferation, Genetic Disorders, Stem cells
