TY - JOUR
T1 - Physiological regulation of the heat shock response by glutamine
T2 - implications for chronic low-grade inflammatory diseases in age-related conditions
AU - Leite, Jaqueline Santos Moreira
AU - Cruzat, Vinicius Fernandes
AU - Krause, Mauricio
AU - Homem de Bittencourt, Paulo Ivo
N1 - Funding Information:
This work and current studies by the authors on this matter have support of fellowships from the São Paulo State Foundation for Research Support (FAPESP, Process: 2015/00446-4 to JSML) and Brazilian National Council for Scientific and Technological Development (CNPq, process #402398/2013-2 and 372373/2013-5 to VFC). CNPq grant support to MSK (#402398/2013-2 and 372373/2013-5) and PIHBJ (#402626/2012-5 and 402364/2012-0) are also acknowledged. The authors disclose research support from Propesq-UFRGS as well.
Funding Information:
The authors dedicate this manuscript to Professor Rui Curi, for his tireless and constant support and true affection. This work and current studies by the authors on this matter have support of fellowships from the S?o Paulo State Foundation for Research Support (FAPESP, Process: 2015/00446-4 to JSML) and Brazilian National Council for Scientific and Technological Development (CNPq, process #402398/2013-2 and 372373/2013-5 to VFC). CNPq grant support to MSK (#402398/2013-2 and 372373/2013-5) and PIHBJ (#402626/2012-5 and 402364/2012-0) are also acknowledged. The authors disclose research support from Propesq-UFRGS as well. All the authors were involved in co-writing the manuscript. PIHBJ, prepared the figures, supervised the elaboration of the manuscript, and wrote its revised final version. All authors read and approved the final manuscript. The authors declare that they have no competing interests. All the authors had final approval of the submitted and published versions of the manuscript.
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/12
Y1 - 2016/12
N2 - Aging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70), which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acid l-glutamine, whose production within the skeletal muscle and liberation into the blood stream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.
AB - Aging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70), which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acid l-glutamine, whose production within the skeletal muscle and liberation into the blood stream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.
KW - Age-related condition
KW - Aging
KW - Exercise
KW - Glutamine
KW - Heat shock response
KW - Hexosamine biosynthetic pathway (HBP)
KW - HSP70
KW - Inflammation
KW - Stress response
UR - http://www.scopus.com/inward/record.url?scp=85050659606&partnerID=8YFLogxK
UR - https://doi.org/10.25905/21555231.v1
U2 - 10.1186/s41110-016-0021-y
DO - 10.1186/s41110-016-0021-y
M3 - Review article
AN - SCOPUS:85050659606
SN - 1519-8928
VL - 41
JO - Nutrire
JF - Nutrire
IS - 1
M1 - 17
ER -
