PARP

The present study investigates the mechanism by which obesity associated rise in leptin and insulin levels cause anovulation in vespertilionid bat, Scotophilus heathii. In the ovary of S. heathii, leptin and insulin receptors were mainly localized in interstitial and thecal cells and in the granulosa cells of primary follicles suggesting its possible role in androgen synthesis and follicular development. Adiposity associated increase in circulating leptin level down regulate ovarian LH-receptor expression and produce characteristic morphological changes in the antral follicles, such as hypertrophy of granulosa cells and a sharp decline in the rate of proliferation as well as apoptosis in the antral follicles. These follicles are referred as unique antral follicle. The in vitro study confirmed the in vivo findings that the high dose of leptin suppresses apoptosis and LH receptors. The present study thus showed that the adiposity associated increase in leptin during the first phase of follicular development inhibits folliculogenesis and simultaneously suppresses both follicular proliferation and apoptosis by reducing sensitivity to gonadotropin stimulation and decreasing circulating LH levels.

C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina platensis is of greater importance because of its various biological and pharmacological properties. It is a water soluble, non-toxic fluorescent protein pigment with potent anti-oxidant, anti-inflammatory and anti-cancer properties. In the present study the effect of highly purified C-PC was tested on growth and multiplication of human chronic myeloid leukemia cell line (K562). The results indicate significant decrease (49%) in the proliferation of K562 cells treated with 50 μM C-PC up to 48 h. Further studies involving fluorescence and electron microscope revealed characteristic apoptotic features like cell shrinkage, membrane blebbing and nuclear condensation. Agarose electrophoresis of genomic DNA of cells treated with C-PC showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 25 and 50 μM C-PC for 48 h showed 14.11 and 20.93% cells in sub-G0/G1 phase, respectively. C-PC treatment of K562 cells also resulted in release of cytochrome c into the cytosol and poly(ADP) ribose polymerase (PARP) cleavage. These studies also showed down regulation of anti-apoptotic Bcl-2 but without any changes in pro-apoptotic Bax and thereby tilting the Bcl-2/Bax ratio towards apoptosis. These effects of C-PC appear to be mediated through entry of C-PC into the cytosol by an unknown mechanism. The present study thus demonstrates that C-PC induces apoptosis in K562 cells by cytochrome c release from mitochondria into the cytosol, PARP cleavage and down regulation of Bcl-2.

A compound that can target cells expressing the estrogen receptor (ER), and produce predominantly 3-MeA adducts in those cells has been designed and synthesized. This compound produces mainly the 3-MeA adduct upon reaction with calf thymus DNA, and binds to the ER with a relative binding affinity of 51% (estradiol = 100%). The compound is toxic to ER-expressing MCF-7 breast