TY  - JOUR
A1  - Castro, José Pedro
A1  - Grune, Tilman
A1  - Speckmann, Bodo
T1  - The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
JF  - Biological chemistry
N2  - White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/ release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho) physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e. g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.
KW  - adipogenesis
KW  - adipose tissue dysregulation
KW  - antioxidants
KW  - metabolic disorders
KW  - oxidative stress
Y1  - 2016
U6  - https://doi.org/10.1515/hsz-2015-0305
SN  - 1431-6730
SN  - 1437-4315
VL  - 397
SP  - 709
EP  - 724
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Reeg, Sandra
A1  - Jung, Tobias
A1  - Castro, José Pedro
A1  - Davies, Kelvin J. A.
A1  - Henze, Andrea
A1  - Grune, Tilman
T1  - The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome
JF  - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2  - One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
KW  - Protein oxidation
KW  - Proteasome
KW  - Chaperone
KW  - HSP70
Y1  - 2016
U6  - https://doi.org/10.1016/j.freeradbiomed.2016.08.002
SN  - 0891-5849
SN  - 1873-4596
VL  - 99
SP  - 153
EP  - 166
PB  - Elsevier
CY  - New York
ER  -