A b s t r a c t Brain-derived neurotrophic factor (BDNF) plays an important role in neuro-nal sur... more A b s t r a c t Brain-derived neurotrophic factor (BDNF) plays an important role in neuro-nal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduc-tion cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.
Objective. The study was conducted to observe whether brain-derived neurotrophic factor (BDNF) ha... more Objective. The study was conducted to observe whether brain-derived neurotrophic factor (BDNF) has cytoprotective actions against alloxan (AL), streptozotocin (STZ), doxorubicin (DB) and benzo(a)pyrene (BP) compounds in vitro that may account for its beneficial action in diabetes mellitus. Materials and methods. This in vitro study was performed using rat insulinoma (RIN5F) cells. Possible cytoprotective action of BDNF (using pre-treatment, simultaneous and post-treatment schedules of RIN5F cells with BDNF) against the four chemicals tested was evaluated using MTT and apoptosis assays. Possible mechanism of cytoprotective action of BDNF was assessed by measuring BCl2/IKB-β/Pdx mRNA transcripts and anti-oxidant levels in RIN5F cells. Effect of alloxan, STZ, doxorubicin and BP on the production of BDNF by RIN5F cells was also studied. Results. Results of the present study revealed that BDNF in the doses (100 ng > 50 ng > 10 ng/ml) has significant cytoprotection (P < 0.001, P < 0.01) on cytotoxic action of AL, STZ, DB and BP against rat insulinoma RIN5F (5 × 10 4 cells/100 μl) cells in vitro. It was observed that AL, STZ, DB and BP inhibited BDNF production significantly (P < 0.001) in a dose-dependent manner by RIN5F cells (0.5 × 10 6 cells/500 μl) in vitro, while BDNF not only prevented apoptosis induced by these four chemicals but also significantly increased (P < 0.001) BCl2/IKB-β/Pdx mRNA transcripts and restored anti-oxidant levels (P < 0.01) in RIN5F cells to normal. Discussion. These results suggest that BDNF has potent cytoprotective actions, restores anti-oxidant defenses to normal and thus, prevents apoptosis and preserves insulin secreting capacity of β cells. In addition, BDNF enhanced viability of RIN 5F in vitro. Thus, BDNF not only has anti-diabetic actions but also preserves pancreatic β cells integrity and enhances their viability. These results imply that BDNF functions as an endogenous cytoprotective molecule that may explain its beneficial actions in some neurological conditions as well.
A b s t r a c t Brain-derived neurotrophic factor (BDNF) plays an important role in neuro-nal sur... more A b s t r a c t Brain-derived neurotrophic factor (BDNF) plays an important role in neuro-nal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduc-tion cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.
Objective. The study was conducted to observe whether brain-derived neurotrophic factor (BDNF) ha... more Objective. The study was conducted to observe whether brain-derived neurotrophic factor (BDNF) has cytoprotective actions against alloxan (AL), streptozotocin (STZ), doxorubicin (DB) and benzo(a)pyrene (BP) compounds in vitro that may account for its beneficial action in diabetes mellitus. Materials and methods. This in vitro study was performed using rat insulinoma (RIN5F) cells. Possible cytoprotective action of BDNF (using pre-treatment, simultaneous and post-treatment schedules of RIN5F cells with BDNF) against the four chemicals tested was evaluated using MTT and apoptosis assays. Possible mechanism of cytoprotective action of BDNF was assessed by measuring BCl2/IKB-β/Pdx mRNA transcripts and anti-oxidant levels in RIN5F cells. Effect of alloxan, STZ, doxorubicin and BP on the production of BDNF by RIN5F cells was also studied. Results. Results of the present study revealed that BDNF in the doses (100 ng > 50 ng > 10 ng/ml) has significant cytoprotection (P < 0.001, P < 0.01) on cytotoxic action of AL, STZ, DB and BP against rat insulinoma RIN5F (5 × 10 4 cells/100 μl) cells in vitro. It was observed that AL, STZ, DB and BP inhibited BDNF production significantly (P < 0.001) in a dose-dependent manner by RIN5F cells (0.5 × 10 6 cells/500 μl) in vitro, while BDNF not only prevented apoptosis induced by these four chemicals but also significantly increased (P < 0.001) BCl2/IKB-β/Pdx mRNA transcripts and restored anti-oxidant levels (P < 0.01) in RIN5F cells to normal. Discussion. These results suggest that BDNF has potent cytoprotective actions, restores anti-oxidant defenses to normal and thus, prevents apoptosis and preserves insulin secreting capacity of β cells. In addition, BDNF enhanced viability of RIN 5F in vitro. Thus, BDNF not only has anti-diabetic actions but also preserves pancreatic β cells integrity and enhances their viability. These results imply that BDNF functions as an endogenous cytoprotective molecule that may explain its beneficial actions in some neurological conditions as well.
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