Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments

نویسندگان

  • Linda V. Hjørnevik
  • Lise Fismen
  • Fiona M. Young
  • Therese Solstad
  • Kari E. Fladmark
چکیده

Apoptotic cell death is induced in primary hepatocytes by the Ser/Thr protein phosphatase inhibiting cyanobacterial toxin nodularin after only minutes of exposure. Nodularin-induced apoptosis involves a rapid development of reactive oxygen species (ROS), which can be delayed by the Ca2+/calmodulin protein kinase II inhibitor KN93. This apoptosis model provides us with a unique population of highly synchronized dying cells, making it possible to identify low abundant phosphoproteins participating in apoptosis signaling. Here, we show that nodularin induces phosphorylation and possibly also cysteine oxidation of the antioxidant Cu,Zn superoxide dismutase (SOD1), without altering enzymatic SOD1 activity. The observed post-translational modifications of SOD1 could be regulated by Ca2+/calmodulin protein kinase II. In untreated hepatocytes, a high concentration of SOD1 was found in the sub-membranous area, co-localized with the cortical actin cytoskeleton. In the early phase of nodularin exposure, SOD1 was found in high concentration in evenly distributed apoptotic buds. Nodularin induced a rapid reorganization of the actin cytoskeleton and, at the time of polarized budding, SOD1 and actin filaments no longer co-localized.

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

Heat shock protein 70 protects motor neuronal cells expressing mutant Cu/Zn superoxide dismutase (SOD1) against altered calcium homeostasis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons leading to paralysis and death. Mutations of the human Cu/Zn superoxide dismutase (SOD1) are found in some cases of familial ALS (fALS). Recent evidences suggest the accumulation of intracellular calcium is one of the primary mechanisms of motor neuronal degeneration. In th...

متن کامل

Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria.

The antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) is predominantly localized in the cytosol, but it is also found in mitochondria. Studies in yeast suggest that apoSOD1 is imported into mitochondria and trapped inside by folding and maturation, which is facilitated by its copper chaperone for SOD1 (CCS). Here, we show that in mammalian cells, SOD1 mitochondrial localization is dictated b...

متن کامل

Heat shock protein 70 protects motor neuronal cells expressing mutant Cu/Zn superoxide dismutase (SOD1) against altered calcium homeostasis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive loss of motor neurons leading to paralysis and death. Mutations of the human Cu/Zn superoxide dismutase (SOD1) are found in some cases of familial ALS (fALS). Recent evidences suggest the accumulation of intracellular calcium is one of the primary mechanisms of motor neuronal degeneration. In th...

متن کامل

Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signalling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to prom...

متن کامل

Association of CAT C-262T and SOD1 A251G single nucleotide polymorphisms susceptible to gastric cancer

Oxidative stress is known to be one of the major factors involved in the development and progression of cancer. Oxidative stress can occur due to an imbalance between concentrations of reactive oxygen species and antioxidant capacities. Catalase (CAT; OMIM 115500) and superoxide dismutase 1 (SOD1; OMIM 147450) play important roles in the primary defense against oxidative stress. In the present ...

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:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2012