scholarly journals Pharmacological and Molecular Evidence of Neuroprotective Curcumin Effects Against Biochemical and Behavioral Sequels Caused by Methamphetamine: Possible Function of CREB-BDNF Signaling Pathway

2021 ◽  
Author(s):  
Mina Gholami ◽  
◽  
Farzad Hozuri ◽  
Setayesh Abdolkarimi ◽  
Mahsa Mahmoudi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Interleukin 1 ◽  
Male Rats ◽  
Molecular Evidence ◽  
Necrosis Factor Alpha ◽  
Multiple Parameters ◽  
Pathway Activation ◽  
Factor Alpha ◽  
Bdnf Signaling ◽  
Induced Apoptosis

The neuroprotective impact of curcumin and the role of CREB-BDNF signaling in this way was evaluated in methamphetamine (METH)-induced neurodegeneration in rats. Sixty adult male rats were randomly split into 6 groups. While normal saline and 10 mg / kg METH were administered intraperitoneally in Groups 1 and 2, Groups 3, 4, 5 and 6 received METH (10 mg/kg) and Curcumin (10, 20, 40 and 80 mg/kg respectively) simultaneously. Morris Water Maze (MWM), oxidative hippocampal, antioxidant, inflammatory, apoptotic, and CREB and BDNF were assessed. We've found that METH disturbs learning and memory. Concurrent curcumin therapy (40 and 80 mg / kg) decreased cognitive disturbance caused by METH. Multiple parameters, such as lipid peroxidation, oxidized form of glutathione (GSSG), interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and Bax, increased by METH therapy, although the reduced type of glutathione (GSH), Bcl-2, P-CREB and BDNF concentrations in the hippocampus decreased. Different doses of curcumin adversely attenuated METH-induced apoptosis, oxidative stress and inflammation, but enhanced concentrations of P-CREB and BDNF. Curcumin-caused neuroprotection against METH-induced neurodegeneration is conducted by P-CREB / BDNF signaling pathway activation.

scholarly journals Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis.

1996 ◽  
Vol 184 (2) ◽  
pp. 717-724 ◽  
Author(s):  
R M Friedlander ◽  
V Gagliardini ◽  
R J Rotello ◽  
J Yuan
Keyword(s):  
Cell Death ◽  
Neutralizing Antibodies ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Converting Enzyme ◽  
Necrosis Factor Alpha ◽  
Trophic Factor Deprivation ◽  
Cell Death Gene ◽  
Factor Alpha ◽  
Induced Apoptosis

Prointerleukin-1 beta (pro-IL-1 beta) is the only known physiologic substrate of the interleukin-1 beta (IL-1 beta)-converting enzyme (ICE), the founding member of the ICE/ced-3 cell death gene family. Since secreted mature IL-1 beta has been detected after apoptosis, we investigated whether this cytokine, when produced endogenously, plays a role in cell death. We found that hypoxia-induced apoptosis can be inhibited by either the IL-1 receptor antagonist (IL-1Ra) or by neutralizing antibodies to IL-1 or to its type 1 receptor. IL-1Ra also inhibits apoptosis induced by trophic factor deprivation in primary neurons, as well as by tumor necrosis factor alpha in fibroblasts. In addition, during the G1/S phase arrest, mature IL-1 beta induces apoptosis through a pathway independent of CrmA-sensitive gene activity. We also demonstrate that Ice, when expressed in COS cells, requires the coexpression of pro-IL-1 beta for the induction of apoptosis, which is inhibited by IL-1Ra. Interestingly, we found that mature IL-1 beta has antiapoptotic activity when added exogenously before the onset of hypoxia, which we found is caused in part by its ability to downregulate the IL-1 receptor. Our findings demonstrate that pro-IL-1 beta is a substrate of ICE relevant to cell death, and depending on the temporal cellular commitment to apoptosis, mature IL-1 beta may function as a positive or negative mediator of cell death.

scholarly journals Insoluble glycogen, a metabolizable internal adsorbent, decreases the lethality of endotoxin shock in rats

1997 ◽  
Vol 6 (5-6) ◽  
pp. 319-322
Author(s):  
S. Sipka ◽  
G. Bot ◽  
P. Gergely ◽  
L. Bertók ◽  
J. Csongor ◽  
...  
Keyword(s):  
Binding Capacity ◽  
Interleukin 1 ◽  
Endotoxin Shock ◽  
Tumour Necrosis Factor Alpha ◽  
Male Rats ◽  
Necrosis Factor Alpha ◽  
Naturally Occurring ◽  
Factor Alpha ◽  
Necrosis Factor

Insoluble glycogen is an enzymatically modified form of naturally occurring soluble glycogen with a great adsorbing capacity. It can be metabolized by phagocytes to glucose. In this study we used insoluble glycogen intravenously in the experimental endotoxin shock of rats. Wistar male rats were sensitized to endotoxin by Pb acetate. The survival of rats were compared in groups of animals endotoxin shock treated and non-treated with insoluble glycogen. Furthermore, we have determinedin vitrothe binding capacity of insoluble glycogen for endotoxin, tumour necrosis factor alpha, interleukin-1 and secretable phospholipase A2. Use of 10 mg/kg dose of insoluble glycogen could completely prevent the lethality of shock induced by LD50quantity of endotoxin in rats. All animals treated survived. Insoluble glycogen is a form of ‘metabolizable internal adsorbents’. It can potentially be used for treatment of septic shock.

Pancreatic beta-cell-selective production of tumor necrosis factor-alpha induced by interleukin-1

Diabetes ◽  
1993 ◽  
Vol 42 (7) ◽  
pp. 1026-1031 ◽  
Author(s):  
K. Yamada ◽  
N. Takane ◽  
S. Otabe ◽  
C. Inada ◽  
M. Inoue ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Beta Cell ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Pancreatic Beta Cell ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Differential effects of cytokines on thermosensitive neurons in guinea pig preoptic area slices

1991 ◽  
Vol 261 (5) ◽  
pp. R1096-R1103 ◽  
Author(s):  
M. Shibata ◽  
C. M. Blatteis
Keyword(s):  
Guinea Pig ◽  
Preoptic Area ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Firing Rates ◽  
Artificial Cerebrospinal Fluid ◽  
Cold Sensitive ◽  
Factor Alpha ◽  
Necrosis Factor

This study was undertaken to determine whether the reported different courses of the febrile responses to the cytokines interleukin-1 beta (IL-1), interferon-alpha 2 (IFN), and tumor necrosis factor-alpha (TNF) might have neuroelectrophysiological correlates. The reactions of individual thermosensitive neurons in the preoptic area (POA) were evaluated by recording their extracellular single-unit firing rates (FR) in slices of guinea pig POA perfused with artificial cerebrospinal fluid (aCSF), human recombinant IL-1 (50-500 ng), IFN (1,000-8,000 U), and TNF (400-5,000 ng) (all doses per min/ml aCSF); thermosensitivity was assessed by FR responses to changes of perfusate temperature (32-42 degrees C). Overall, these cytokines depressed the FR of warm-sensitive units and excited those of cold-sensitive units, in agreement with expectations. However, the responses of individual neurons treated with two or all three cytokines were dissimilar: 61% of the units tested reacted differentially to two or three cytokines, 32% exhibited identical responses, and 7% had no response to any cytokine. These results support the possibility that IL-1, IFN, and TNF may affect not the same but rather distinct neurons functionally connected to common pyrogenic effectors. Thus they suggest that differential neuronal substrates may be utilized by each cytokine to exert its pyrogenic effect.

scholarly journals Transcription Factor AP-2α Is Preferentially Cleaved by Caspase 6 and Degraded by Proteasome during Tumor Necrosis Factor Alpha-Induced Apoptosis in Breast Cancer Cells

2001 ◽  
Vol 21 (15) ◽  
pp. 4856-4867 ◽  
Author(s):  
Okot Nyormoi ◽  
Zhi Wang ◽  
Dao Doan ◽  
Maribelis Ruiz ◽  
David McConkey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Caspase 6 ◽  
Induced Apoptosis ◽  
Necrosis Factor

ABSTRACT Several reports have linked activating protein 2α (AP-2α) to apoptosis, leading us to hypothesize that AP-2α is a substrate for caspases. We tested this hypothesis by examining the effects of tumor necrosis factor alpha (TNF-α) on the expression of AP-2 in breast cancer cells. Here, we provide evidence that TNF-α downregulates AP-2α and AP-2γ expression posttranscriptionally during TNF-α-induced apoptosis. Both a general caspase antagonist (zVADfmk) and a caspase 6-preferred antagonist (zVEIDfmk) inhibited TNF-α-induced apoptosis and AP-2α downregulation. In vivo tests showed that AP-2α was cleaved by caspases ahead of the DNA fragmentation phase of apoptosis. Recombinant caspase 6 cleaved AP-2α preferentially, although caspases 1 and 3 also cleaved it, albeit at 50-fold or higher concentrations. Activated caspase 6 was detected in TNF-α-treated cells, thus confirming its involvement in AP-2α cleavage. All three caspases cleaved AP-2α at asp19 of the sequence asp-arg-his-asp (DRHD19). Mutating D19 to A19abrogated AP-2α cleavage by all three caspases. TNF-α-induced cleavage of AP-2α in vivo led to AP-2α degradation and loss of DNA-binding activity, both of which were prevented by pretreatment with zVEIDfmk. AP-2α degradation but not cleavage was inhibited in vivo by PS-431 (a proteasome antagonist), suggesting that AP-2α is degraded subsequent to cleavage by caspase 6 or caspase 6-like enzymes. Cells transfected with green fluorescent protein-tagged mutant AP-2α are resistant to TNF-α-induced apoptosis, further demonstrating the link between caspase-mediated cleavage of AP-2α and apoptosis. This is the first report to demonstrate that degradation of AP-2α is a critical event in TNF-α-induced apoptosis. Since the DRHD sequence in vertebrate AP-2 is widely conserved, its cleavage by caspases may represent an important mechanism for regulating cell survival, proliferation, differentiation, and apoptosis.

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