Heat shock proteins 27 and 70 regulating angiotensin II-induced NF-κB: a possible connection to blood pressure control?

2008 ◽  
Vol 33 (5) ◽  
pp. 1042-1049 ◽  
Author(s):  
Tracy S. Voegeli ◽  
Amanda J. Wintink ◽  
Yu Chen ◽  
R. William Currie

Heat shock proteins (HSPs) are critical for cell survival and have several mechanisms of action. HSPs regulate protein folding, suppress apoptosis, and regulate anti-oxidative activity. In addition, HSPs are involved in the regulation of the pro-inflammatory transcription factor nuclear factor (NF)-κB. When angiotensin (Ang) II is infused into rats, there is a significant increase in systolic blood pressure, and NF-κB is activated in the heart. If rats are heat shocked to induce the heat shock response and HSPs before Ang II infusion, there is a significant suppression of both the Ang II-induced increase in blood pressure and NF-κB activation in the heart. Although the role of specific HSPs in the regulation of NF-κB is unclear, several HSPs, including Hsp27 and Hsp70, are thought to be involved in the regulation of Ang II-induced NF-κB. The role of Hsp27 and Hsp70 in NF-κB activation is reviewed here, along with evidence suggesting that HSPs regulate Ang II-induced blood pressure through the regulation of NF-κB.

2021 ◽  
Author(s):  
Ruben Bulkescher ◽  
Thomas Fleming ◽  
Claus Rodemer ◽  
Rebekka Medert ◽  
Marc Freichel ◽  
...  

Increased metabolic flux produces potentially harmful side-products, such as reactive dicarbonyl and oxygen species. The reactive dicarbonly methylglyoxal (MG) can impair oxidative capacity, which is downregulated in type 2 diabetes. Heat shock proteins (HSPs) of subfamily A (Hsp70s) promote ATP-dependent processing of damaged proteins during MG exposure which also involve mitochondrial proteins. Since the protection of mitochondrial proteins could promote higher production of reactive metabolites due to increased substrate flux, tight regulation of HspA-mediated protein handling is important. We hypothesized that stress-inducible HspAs (HspA1A/HspA1B) are pivotal for maintaining mitochondrial biogenesis during acute MG-stress. To analyze the role of stress-inducible HspA1A/HspA1B for maintenance of mitochondrial homeostasis during acute MG exposure, we knocked out HSPA1A/HSPA1B in mouse endothelial cells. HSPA1A/HSPA1B KO cells showed upregulation of the mitochondrial chaperones HspA9 (mitochondrial Hsp70/mortalin) and HspD1 (Hsp60) as well as induction of mitochondrial biogenesis upon MG exposure. Increased mitochondrial biogenesis was reflected by elevated mitochondrial branching, total count and area as well as by upregulation of mitochondrial proteins and corresponding transcription factors. Our findings suggest that mitochondrial HspA9 and HspD1 promote mitochondrial biogenesis during acute MG stress, which is counterregulated by HspA1A/HspA1B to prevent mitochondrial overstimulation and to maintain balanced oxidative capacity under metabolic stress conditions. These data support an important role of HSPs in MG-induced hormesis.


FEBS Letters ◽  
1999 ◽  
Vol 448 (2-3) ◽  
pp. 265-268 ◽  
Author(s):  
Ilia V Manukhov ◽  
Gennadii E Eroshnikov ◽  
Mikhail Yu Vyssokikh ◽  
Gennadii B Zavilgelsky

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