Figure 20.

A possible model of cell destination via CD38 and PARP. NAD⁺ is catalyzed to form cADPR by CD38. Ca²⁺ mobilization is caused by cADPR, leading to cell functioning such as insulin secretion. DNA breaks induce PARP activation, leading to cell death (necrosis) via NAD⁺ depletion. When PARP acts as a transcription factor, Reg genes/proteins are expressed for cell regeneration/proliferation. It should be noted here that nicotinamide, a PARP inhibitor, prolongs survival of primary cultured hepatocytes without involving loss of hepatocyte-specific functions.²⁹⁴⁾