Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease

Abstract

Apoptosis is a carefully orchestrated and tightly controlled form of cell death, conserved across metazoans. As the executioners of apoptotic cell death, cysteine-dependent aspartate-directed proteases (caspases) are critical drivers of this cellular disassembly. Early studies of genetically programmed cell death demonstrated that the selective activation of caspases induces apoptosis and the precise elimination of excess cells, thereby sculpting structures and refining tissues. However, over the past decade there has been a fundamental shift in our understanding of the roles of caspases during cell death—a shift precipitated by the revelation that apoptotic cells actively engage with their surrounding environment throughout the death process, and caspases can trigger a myriad of signals, some of which drive concurrent cell proliferation regenerating damaged structures and building up lost tissues. This caspase-driven compensatory proliferation is referred to as apoptosis-induced proliferation (AiP). Diverse mechanisms of AiP have been found across species, ranging from planaria to mammals. In this review, we summarize the current knowledge of AiP and we highlight recent advances in the field including the involvement of reactive oxygen species and macrophage-like immune cells in one form of AiP, novel regulatory mechanisms affecting caspases during AiP, and emerging clinical data demonstrating the critical importance of AiP in cancer.

Microglial Corpse Clearance: Lessons From Macrophages

“…Similarly, the secretome of phagocytic microglia acutely inhibits proliferation of neural progenitors, allowing their longterm maintenance and the preservation of neurogenesis. These feedback mechanisms are likely related to the compensatory proliferation induced by killer caspases during apoptosis ("apoptosis-induced proliferation, " AiP), observed in some cell types and organisms (121). Because of these loops between death and life processes, the identification of phagoptosis must not be procedural, i.e., phagocytosis blockade increases survival, ergo, phagocytosis must kill cells.…”

Detecting Anastasis <em>In Vivo</em> by CaspaseTracker Biosensor

“…While caspase activity has been traditionally assumed as a hallmark of apoptosis, growing studies reveal that non-apoptotic caspase activity plays potential roles in diverse normal cell functions, such as regulation of neuronal activity 79,80 , learning and memory 81,82,83,84 , suppression of necroptotic cell death 85,86 , spermatid individualization 87,88 , microRNA processing 89 , cell proliferation 90 , and cell fate patterning 91 . In addition to apoptosis and anastasis, the CaspaseTracker biosensor system can therefore detect non-apoptotic caspase activity, which is present in the brain and optic lobes, cardia, gut, Malpighian tubules, trachea, muscles, and other tissues of Drosophila 19,46,64 .…”

Efek Sinergis Kombinasi Ekstrak Air Akar Batu (Gerrardanthus Macrorhizus) dengan Doxorubicin pada Sel Kanker Payudara T47D

“…Perubahan morfologi menjadi shrinkaged dan rounded cells (menyusut dan membulat) adalah salah satu indikator awal terjadinya apoptosis. 20 Berdasarkan hasil MTT assay, perlakuan GM mengakibatkan sel T47D masih viable (>90%), namun memperlihatkan karakteristik morfologi yang mengindikasikan terjadinya aktivasi apoptosis. Apoptosis terkait dengan hampir seluruh proses fundamental dalam kehidupan, baik pada kondisi fisiologis maupun patologis.…”

“…Sebagai salah satu jenis kematian sel terprogram, apoptosis menunjukkan desain seluler yang sangat urut dan teratur. 20 Hambatan dalam proses apoptosis menyebabkan proliferasi terjadi secara terus menerus. Kemampuan sel untuk selalu memelihara signal proliferasi dan mengabaikan signal apoptosis merupakan karakteristik sel kanker.…”