Cell Death Mode Switch from Necrosis to Apoptosis in Brain

Abstract

In brain ischemia, cell destructive necrosis occurs in the core, which in turn links to cell death expansion in the vicinity. Apoptosis, on the other hand, occurs in the surroundings of the core, called the penumbra, several days later. As cells showing apoptosis disappear by microglial phagocytosis in the brain, cell death induced by ischemic stress should eventually be terminated. Thus, the authors propose the hypothesis that the cell death mode switch in the event of brain ischemia is an in vivo self-protective mechanism. The authors attempt to overview the current understanding of the molecular mechanisms of necrosis and apoptosis in relation to the ATP hypothesis, and also introduce novel mechanisms for an in vitro cell death mode switch.

Prothymosin-α1 prevents necrosis and apoptosis following stroke

“…APO1 death receptor was not induced, indicating a cell-type specificity for gene transcription and, in agreement with previous results, 6 p21 Waf1 was not upregulated. Furthermore, the involvement of apoptotic intrinsic pathway was shown by induction of Noxa (Figure 1d).…”

“…was given to rats 30 min after reperfusion, and proteins (30 mg) from the cortex isolated 2.5 h later were used for Western blot analysis Following stroke or traumatic damages, both necrotic and apoptotic neuronal death cause loss of functions including memory, sensory perception and motor skills. 4,5 Necrosis occurs during the early stages of stroke and of the affected area expands with time, 6 whereas the apoptosis occurs with some delay, but may also have a potential role in restricting the spread of irretrievable damage. 6,7 There have been many attempts to find compounds that inhibit apoptosis, but the protective potencies of these compounds against ischemic damage in vivo remain limited.…”

“…4,5 Necrosis occurs during the early stages of stroke and of the affected area expands with time, 6 whereas the apoptosis occurs with some delay, but may also have a potential role in restricting the spread of irretrievable damage. 6,7 There have been many attempts to find compounds that inhibit apoptosis, but the protective potencies of these compounds against ischemic damage in vivo remain limited. [8][9][10][11] This may be related to the possibility that rapid and expanding necrosis largely contributes to the total loss of brain neurons following ischemia.…”

“…[11][12][13] Compared with the machinery involved in apoptosis, necrosis is a more passive process, in which energy failure leads to a rupture of the plasma membrane with concomitant loss of intracellular proteins and ions. 6 However, no compounds that inhibit necrosis are known. Here, we demonstrate that ProTa has potential therapeutic utility against the necrosis component of stroke.…”

“…Indeed, in old RBCs, both protein levels and the in vitro activity of TG2 are increased. 6 In addition, transglutaminase-catalyzed polymers were isolated from patients with Kö ln disease 4 or sickle cell anemia 4 diseases in which the lifespan of RBCs is known to be greatly reduced. Nevertheless, the physiological role of TG2 in the erythrocyte aging process still remains unclear.…”