RNA interference links oxidative stress to the inhibition of heat stress adaptation.

نویسندگان

  • Zoltán Spiró
  • Mehmet Alper Arslan
  • Milán Somogyvári
  • Minh Tu Nguyen
  • Arne Smolders
  • Balázs Dancsó
  • Nóra Németh
  • Zsuzsanna Elek
  • Bart P Braeckman
  • Péter Csermely
  • Csaba Sőti
چکیده

UNLABELLED Increased oxidative stress is associated with various diseases and aging, while adaptation to heat stress is an important determinant of survival and contributes to longevity. However, the impact of oxidative stress on heat resistance remains largely unclear. AIM In this study we investigated how oxidative stress impinges on heat stress responses. RESULTS We report that hydrogen-peroxide (H(2)O(2)) pretreatment inhibits both acquired thermotolerance and heat-induced Hsp70 expression in mammalian cells, as well as acquired thermotolerance in the nematode Caenorhabditis elegans, via RNA interference. Moreover, we demonstrate that elimination of RNA interference by silencing key enzymes in microRNA biogenesis, dcr-1 or pash-1, restores the diminished intrinsic thermotolerance of aged and H(2)O(2)-elimination compromised (catalase-2 and peroxiredoxin-2 deficient) worms. INNOVATION AND CONCLUSION These results uncover a novel post-transcriptional element in the regulation of heat stress adaptation under oxidative conditions that may have implications in disease susceptibility and aging.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The bromodomain protein BRD4 regulates splicing during heat shock

The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes and a partial inhibition of splicing. These features closely resemble the proteotoxic stress response during tumor development. The bromodomain protein BRD4 has been identified as an integral member of the oxidative ...

متن کامل

Natural Variation for Lifespan and Stress Response in the Nematode Caenorhabditis remanei

Genetic approaches (e.g. mutation, RNA interference) in model organisms, particularly the nematode Caenorhabditis elegans, have yielded a wealth of information on cellular processes that can influence lifespan. Although longevity mutants discovered in the lab are instructive of cellular physiology, lab studies might miss important genes that influence health and longevity in the wild. C. elegan...

متن کامل

Welcome to the Klenk Symposium 2016

In recent years the bromodomain protein BRD4 has gained extensive attention – mainly due to its involvement in tumour growth and its widespread success as therapeutic target in leukaemia, lung cancer, melanoma and diverse other tumour entities. Previously we have identified BRD4 as an integral member of the oxidative stress response over the NRF2/KEAP1 axis. We have now extended our analyses an...

متن کامل

PP2A Mediated AMPK Inhibition Promotes HSP70 Expression in Heat Shock Response

BACKGROUND Under stress, AMP-activated protein kinase (AMPK) plays a central role in energy balance, and the heat shock response is a protective mechanism for cell survival. The relationship between AMPK activity and heat shock protein (HSP) expression under stress is unclear. METHODOLOGY/PRINCIPAL FINDINGS We found that heat stress induced dephosphorylation of AMPKα subunit (AMPKα) in variou...

متن کامل

Imexon induces an oxidative endoplasmic reticulum stress response in pancreatic cancer cells.

Oxidative protein folding in the endoplasmic reticulum (ER) requires strict regulation of redox homeostasis. Disruption of the lumenal redox balance induces an integrated ER stress response that is associated with reduced protein translation, increased chaperone activity, and ultimately cell death. Imexon is a small-molecule chemotherapeutic agent that has been shown to bind glutathione (GSH) a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Antioxidants & redox signaling

دوره 17 6  شماره 

صفحات  -

تاریخ انتشار 2012