Heat induced expression of CD95 and its correlation with the activation of apoptosis upon heat shock in rat histiocytic tumor cells

AbstractThe heat shock response is a universal phenomenon and is among the most highly conserved cellular responses. However, BC-8, a rat histiocytoma, fails to mount a heat shock response unlike all other eukaryotic cells. In the absence of induction of heat shock proteins, apoptotic cell death is activated in BC-8 tumor cells upon heat shock. We demonstrate here that stable transformants of BC-8 tumor cells transfected with hsp70 cDNA constitutively express hsp70 protein and are transiently protected from heat induced apoptosis for 6–8 h. In addition heat stress induces CD95 gene expression in these tumor cells. There is a delay in CD95 expression in hsp70 transfected cells suggesting a correlation between the cell surface expression of CD95 and the time of induction of apoptosis in this tumor cell line. Also expression of CD95 antigen appears to inhibit the interaction between heat shock factors and heat shock elements in these cells resulting in the lack of heat shock response

17AAG Treatment Accelerates Doxorubicin Induced Cellular Senescence: Hsp90 Interferes with Enforced Senescence of Tumor Cells.

Contains fulltext : 110962.pdf (publisher's version ) (Open Access)Hsp90 chaperone has been identified as an attractive pharmacological target to combat cancer. However, some metastatic tumors either fail to respond to Hsp90 inhibition or show recovery necessitating irreversible therapeutic strategies. In response to this enforced senescence has been proposed as an alternate strategy. Here, we demonstrate that inhibiting Hsp90 with 17AAG sensitizes human neuroblastoma to DNA damage response mediated cellular senescence. Among individual and combination drug treatments, 17AAG pre-treatment followed by doxorubicin treatment exhibited senescence-like characteristics such as increased nucleus to cytoplasm ratio, cell cycle arrest, SA-beta-gal staining and the perpetual increase in SAHF. Doxorubicin induced senescence signaling was mediated by p53-p21(CIP/WAF-1) and was accelerated in the absence of functional Hsp90. Sustained p16(INK4a) and H3K4me3 expressions correlating with unaffected telomerase activation annulled replicative senescence and appraised stress induced senescence. Despite increases in [(ROS)i] and [(Ca(2+))i], a concomitant increase in cellular antioxidant defense system suggested oxidation independent senescence activation. Sustained activation of survival (Akt) and proliferative (ERK1/2) kinases fosters robustness of cells. Invigorating senescent cells with growth factor or snooping with mTOR or PI3 kinase inhibitors compromised cell survival but not senescence. Intriguingly, senescence-associated secretory factors from the senescence cells manifested established senescence in neuroblastoma, which offers clinical advantage to our approach. Our study discusses tumor selective functions of Hsp90 and discusses irrefutable strategies of Hsp90 inhibition in anticancer treatments

Lack of heat shock response triggers programmed cell death in a rat histiocytic cell line

AbstractStress response is a universal phenomenon. However, a rat histiocytic cell line, BC-8, showed no heat shock response and failed to synthesize heat shock protein 70 (hsp70) upon heat shock at 42°C for 30 min. BC-8 is a clone of AK-5, a rat macrophage tumor line that is adapted to grow in culture and has the same chromosome number and tumorigenic potential as AK-5. An increase in either the incubation temperature or time or both to BC-8 cells leads to loss of cell viability. In addition, heat shock conditions activated apoptotic cell death in these cells as observed by cell fragmentation, formation of nuclear comets, apoptotic bodies, DNA fragmentation and activation of ICE-like cysteine proteases. Results presented here demonstrate that BC-8 cells cannot mount a typical heat shock response unlike all other eukaryotic cells and that in the absence of induction of hsps upon stress, these cells undergo apoptosis at 42°C

Development of a two arm, high energy, high power laser for plasma research in India

We report here work done towards development of a two arm, high energy, high power Nd:phosphate glass laser system. One arm of the laser is proposed to be operated in a long pulse (∼1.5ns pulse duration) with an energy of ∼400 J. Presently, this arm of the laser is operating at energy of ∼100 J after a disc amplifier that amplifies the laser beam of diameter ∼94 mm. After the addition of two more disc amplifiers which are nearing completion, the laser beam will have energy of ∼400 J, with a beam diameter 140 mm, at an intensity of ∼2 GW/cm2. This beam will be converted to its second harmonic using a 2 × 2 array KDP crystals. The second arm, under development, will operate with a hybrid amplification scheme using optical parametric chirped pulse amplification (OPCPA) and conventional amplification using the existing Nd:glass amplifiers to produce 50 TW, 25 J, 500 fs pulse. A tiled triangular pulse compressor is under development for compressing the stretched pulse