Role of PARP in Germ Cell Death and Spermatogenesis

PARP1 is involved in programmed cell death (apoptosis) and necrosis as well [82] (Fig. 12.2). PARP1 is cleaved in two parts by caspase 3, a 25 kDa fragment consisting of DBD N-terminal and an 85 kDa fragment consisting of the AMD and CD C-terminal fragment. As shown in Fig. 12.1, when the DNA-binding domain separates from the automodification and catalytic domains, PARP1 becomes inactive and consequences of apoptosis occur. On the other hand, the short fragment, N-terminal, inhibits other uncleaved PARP, then restrains the activation of PARP1 by cPARP resulting in more consumption of NAD molecule, energy depletion, and necrosis [83]. As shown in Fig. 12.2, exogenous agents such as ROS or a genotoxin may cause DNA damage in a cell. PARP may act in one of three ways: (1) if low DNA damage occurs, PARP can gather the other repair enzymes and repair DNA damage, (2) if high DNA damage exists, PARP is overexpressed and results in ATP/ NAD depletion and necrosis, and (3) after DNA damage and initiation of apoptosis event and caspase-3 activation, PARP cleavage occurs [2] .

Hikim et al. proposed that exogenous agents can activate caspase-dependent cell death pathway. They showed that by increasing scrotal temperature in rats over time, the cascade signals in the mitochondria-dependent cell death pathway including relocation of Bax, translocation of cytochrome C, caspase activation, and PARP cleavage were demonstrated [84]. In support of the association between PARP and caspases, Codelia et al. reported that using a caspase-8 inhibitor and a pan-caspase inhibitor, cPARP decreases and a reduction of germ cells apoptosis takes place [85].

Fig. 12.2 Possible role of PARP in cell death in the event of DNA damage caused by ROS or a genotoxin; PARP targets the damaged site. If high damage occurs, PARP may become overacti-vated resulting in ATP/NAD depletion and necrosis. Apoptosis can also occur through caspase-3 activation and PARP cleavage. If low damage occurs, PARP can recruit other repair enzymes and DNA repair can occur [2]

Fig. 12.2 Possible role of PARP in cell death in the event of DNA damage caused by ROS or a genotoxin; PARP targets the damaged site. If high damage occurs, PARP may become overacti-vated resulting in ATP/NAD depletion and necrosis. Apoptosis can also occur through caspase-3 activation and PARP cleavage. If low damage occurs, PARP can recruit other repair enzymes and DNA repair can occur [2]

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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