1022-7954/02/3804- $27.00 © 2002
Russian Journal of Genetics, Vol. 38, No. 4, 2002, pp. 345–358. Translated from Genetika, Vol. 38, No. 4, 2002, pp. 437–452.
Original Russian Text Copyright © 2002 by Khlebodarova.
The neurohormonal stress response of an organism
to unfavorable environmental conditions has been dis-
covered more than forty years ago . This is a univer-
sal response to various stimuli inadequate for survival
of an individual population rather than a species as a
whole. As an ancient and evolutionary conserved reac-
tion, stress response develops in organisms, whose evo-
lutionary pathways diverged many million years ago.
Under stressful conditions, protective response is
developed in the whole body and each individual cell
[2, 3]. In
, both cellular and neurohumoral
reactions to stress proved to be under a common genetic
control [4–6]. At the same time, the heat shock response
proved to be induced through independent signaling
pathways [5–8]. The question arises whether there are
heat-shock-activated signaling pathways which are not
involved in the induction of the heat shock response.
Analysis of the mechanisms and pathways of cell shock
given in this review provides an answer to this question.
CELLULAR HEAT SHOCK RESPONSE
The essence of cellular heat shock response is that
after exposure to heat stress the cell discontinues syn-
thesis of most proteins to initiate synthesis of a distinct
set of proteins referred to as heat-shock proteins (HSP).
This nonspeciﬁc reaction is produced in response to
various factors (heat, cold, hypoxia, changes in medium
pH, ions of heavy metals, UV- and X-rays, infection,
inﬂammation, viral toxins, aging etc). According to
contemporary data, the HSP proteins are synthesized
after exposure to all forms of stress described so far
[2, 3, 9, 10].
Ritossa  was the ﬁrst to reveal heat-induced
polytene chromosomes. Later,
pufﬁng was shown to result from transcription activa-
tion of the HSP genes . Numerous studies showed
that HSPs play an important role in protecting cells
from stressful factors. That was conﬁrmed by a phe-
nomenon of induced thermotolerance, when preexpo-
sure of cells or whole organisms to a moderate stress
led to their enhanced survival under conditions of sub-
sequent severe stress . Moreover, the degree of
thermotolerance was correlated with accumulation of
the HSP70, as well as further attenuation of thermotol-
erance occurred in parallel with a decrease in the
amount of this protein . As shown in a number of
studies, thermotolerance is related to the presence of
both low- and high-molecular-weight HSPs [15–20].
What are the heat-shock proteins and the mecha-
nisms through which they protect cells from heat and
other types of stress?
AND THEIR FUNCTION IN A CELL
HSPs are known to be synthesized in response to
stress in all species, from bacteria to humans. Although
HSPs are species-speciﬁc, they are clearly divided into
three groups differing in molecular weight and func-
tions in a cell: (1) a group of high-molecular-weight
proteins with molecular weights of 104, 90, or 83 kDa
in yeast, mammals, and
, respectively; (2) a
family of proteins with molecular weight of about 70 kDa;
and (3) so called small HSPs with molecular weight
ranging from 15 to 30 kDa, including mammalian
-crystallins [9, 10, 12, 18]. Each of these groups
comprise proteins with speciﬁc spectrum of multiple
functions in a cell and speciﬁc tissue and ontogenetic
expression under both normal [12, 18, 21–27] and
stressful conditions [28, 29]. However, all of them
share a common function: they protect a cell from unfa-
vorable agents, though through different mechanisms.
Note that unlike other species, normally developing
displayed no HSP-70 expression ,
whereas in mammals, this protein family participates in
many cellular processes, such as assembly and stabili-
zation of protein molecules as well as their transport
through mitochondrial membranes and nuclear enve-
lope [31–36]. They are involved in signal transduction
, a member of the HSP70 family plays a key role in
cell cycle regulation during gametogenesis [37–39].
How Cells Protect Themselves against Stress?
T. M. Khlebodarova
Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, 630090 Russia;
Received April 9, 2001
—The current evidence on the mechanisms underlying cell response to heat shock is reviewed. The
response dynamics, induction, and attenuation as well as heat shock proteins and the mechanisms through
which they protect cells from stress are considered. The role of these proteins in regulating the signaling cas-
cades, including apoptosis suppression, is shown.