Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Agarwal, Ashok; Mahfouz, R.; Sharma, Rakesh K.; Sarkar, Oli; Mangrola, Devna; Mathur, Premendu P.

doi:10.1186/1477-7827-7-143

Cited by 116 publications

(93 citation statements)

References 219 publications

(291 reference statements)

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“…The association between sDF and apoptosis also was investigated by using another apoptotic marker, the cleaved form of PARP (cPARP), (12,47). Figure 5A reports a typical dot plot showing the immunofluorescent detection of cPARP in TUNEL-labeled sperm.…”

Section: E C H a N I S M S O F S P E R M D N A F R A G M E N T A T I Omentioning

confidence: 99%

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

Muratori

Tamburrino

Marchiani

et al. 2015

Mol Med

209

167

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Sperm DNA fragmentation (sDF) represents a threat to male fertility, human reproduction and the health of the offspring. The causes of sDF are still unclear, even if apoptosis, oxidative assault and defects in chromatin maturation are hypothesized. Using multicolor flow cytometry and sperm sorting, we challenged the three hypothesized mechanisms by simultaneously evaluating sDF and signs of oxidative damage (8-hydroxy, 2'-deoxyguanosine and malondialdehyde [MDA]), apoptosis (caspase activity and cleaved poly[ADP-ribose] polymerase [cPARP]) and sperm immaturity (creatine phosphokinase [CK] and excess of residual histones). Active caspases and c-PARP were concomitant with sDF in a high percentage of spermatozoa (82.6% ± 9.1% and 53.5% ± 16.4%, respectively). Excess of residual histones was significantly higher in DNA-fragmented sperm versus sperm without DNA fragmentation (74.8% ± 17.5% and 37.3% ± 16.6%, respectively, p < 0.005), and largely concomitant with active caspases. Conversely, oxidative damage was scarcely concomitant with sDF in the total sperm population, at variance with live sperm, where 8-OHdG and MDA were clearly associated to sDF. In addition, most live cells with active caspase also showed 8-OHdG, suggesting activation of apoptotic pathways in oxidative-injured live cells. This is the first investigation on the origin of sDF directly evaluating the simultaneous presence of the signs of the hypothesized mechanisms with DNA breaks at the single cell level. The results indicate that the main pathway leading to sperm DNA breaks is a process of apoptosis, likely triggered by an impairment of chromatin maturation in the testis and by oxidative stress during the transit in the male genital tract. These findings are highly relevant for clinical studies on the effects of drugs on sDF and oxidative stress in infertile men and for the development of new therapeutic strategies.

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Section: E C H a N I S M S O F S P E R M D N A F R A G M E N T A T I Omentioning

confidence: 99%

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

Muratori

Tamburrino

Marchiani

et al. 2015

Mol Med

209

167

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“…It possesses antiproliferative, anticarcinogenic and chemopreventive potential (1,2). The antitumor efficacy of curcumin has been documented in animal models as well as in phase I clinical trials with multiple cancer types (3)(4)(5)(6)(7). The molecular targets and therapeutics of curcumin in health and disease have been studied before (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…The antitumor efficacy of curcumin has been documented in animal models as well as in phase I clinical trials with multiple cancer types (3)(4)(5)(6)(7). The molecular targets and therapeutics of curcumin in health and disease have been studied before (5)(6)(7). These studies have reported that curcumin had biological and medicinal properties as well as anticancer potential in preclinical and clinical studies.…”

Section: Introductionmentioning

confidence: 99%

“…The DNA damage includes double-strand breaks (DSB), single strand breaks, base damage, bulky adducts, intra/interstrand cross links, and breakdown of replication fork lesions where one of the key proteins in the base excision repair pathway is the Poly adenosine diphosphate ribose polymerase-1 (PARP-1) (6,19,(32)(33)(34). PARP-1 is a 116-kDa nuclear protein that appears to be involved in DNA repair predominantly in response to environmental stress (32,33).…”

Section: Introductionmentioning

confidence: 99%

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Effect of curcumin on irradiated and estrogen-transformed human breast cell lines

Calaf

Echiburú-Chau²,

Wen³

et al. 2011

Int J Oncol

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Abstract. Curcumin (diferuloyl methane) is a well known antioxidant that exerts antiproliferative and apoptotic effects. Curcumin effect was evaluated in a breast cancer model that was developed using the immortalized breast epithelial cell line MCF-10F after exposure to low doses of high LET (linear energy transfer) α particles (150 keV/µm) of radiation, and subsequently cultured in the presence of 17β-estradiol (estrogen). This model consisted of human breast epithelial cells in different stages of transformation: i) MCF-10F; ii) Estrogen cell line; iii) a malignant Alpha3 cell line; iv) a malignant and tumorigenic, Alpha5 cell line; and v) a cell line derived from Alpha5 injected into the nude mice that gave rise to Tumor2 cell line. Curcumin decreased anchorage-independent growh in transformed breast cancer cell lines in comparison to their counterparts and increased the percentage of cells from G 0 /G 1 with a concomitant increase in G 2 /M phases, as well as a decrease in PCNA and Rho-A protein expression. Among the oncogenes, c-Ha-Ras and Ras homologous A (Rho-A) are important cell signaling factors for malignant transformation and to reach their active GTP bound state, Ras proteins must first release bound GDP mediated by a guanine nucleotide releasing factor (GRF). Then curcumin decrease RasGRF1 protein expression in malignant cell lines. Further, differential expression levels of cleaved (ADP) ribose polymerase 1 (PARP-1) and phosphorylated histone H2AX (γ-H2AX) were observed after curcumin treatment. It seems that PARP-1 similar to H2AX, confers cellular protection against radiation and estrogen-induced DNA damage mediated by curcumin. Therefore, targeting either PARP-1 or H2AX may provide an effective way of maximizing the therapeutic value of antioxidants for cancer prevention.

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“…As we know, one of the most important functions of PARP is to help repair single-stranded DNA nicks, and the cleaved-PARP is critically involved in the intrinsic apoptosis pathway and considered to be a marker of apoptosis. 35,36 In the present study, we observed the expression of proapoptotic and antiapoptotic members of the Bcl-2 family, which is the mitochondrial-related death switch. The members of Bcl-2 homology are divided into three main groups based on function and regions of the domains: multi-domain antiapoptotic proteins (Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1), multi-domain proapoptotic proteins (Bax and Bak), and BH3-only proapoptotic proteins (Bid, PUMA, Bim, and NOXA), trigger the activation of Bak and Bax.…”

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confidence: 72%

PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway

Wen

Liu

Wang³

et al. 2015

IJN

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Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly- l -lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool.

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Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Cited by 116 publications

References 219 publications

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

Investigation on the Origin of Sperm DNA Fragmentation: Role of Apoptosis, Immaturity and Oxidative Stress

Effect of curcumin on irradiated and estrogen-transformed human breast cell lines

PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway

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