On Programmed Cell Death in Plasmodium falciparum: Status Quo

Table 1

Summary of PCD studies in P. falciparum. Symbols indicate the following: Δ—change observed (increase or decrease indicated by ↑ or ↓, resp.); ×—not done. SNAP—S-nitroso-N-acetyl-penicillamine.

Phenotype	Stimulus	Strain	Morphological changes	DNA fragmentation	Mitochondrial membrane potential	Protease involvement	Ref
Apoptosis	Antimalaria drugs	HB3; K1	Δ Microscopy	Δ↑ TUNEL	×	×	[23]
	Bilirubin	NF-54	Δ Fluorescence microscopy	×	Δ↓JC-1 Spectrofluorimetry and fluorescence microscopy	Δ↑ Caspase assay, spectrofluorimetry, DEVD substrate, and DEVD inhibitor	[35]
			×	Δ↑ Laddering, Agarose gel and Southern blotting	×	×	[12]
		3D7	Δ Microscopy	Δ↑ TUNEL by fluorescence microscopy	Δ↓ JC-1 Fluorescence microscopy	Δ VAD inhibitor	[26]
	Chloroquine		×	Δ↑ TUNEL by flow cytometry and fluorescence microscopy	Δ↓ JC-1 Flow cytometry and fluorescence microscopy	Δ↑ Caspase assay, flow cytometry and fluorescence microscopy, VAD substrate, VAD, FA, FF, LLL, CA-074, and E64d inhibitors	[34]
		7G8	Δ Microscopy	Δ↑ TUNEL by fluorescence microscopy	Δ↓ JC-1 fluorescence microscopy	NO CHANGE; VAD inhibitor	[26]
		K1	×	×	Δ↓ JC-1 flow cytometry	×	[34]
	Etoposide	3D7; 7G8		Δ↑ TUNEL by fluorescence microscopy		Δ VAD inhibitor; NO CHANGE; VAD inhibitor	[26]
	Chloroquine	HB3		Δ↑ TUNEL
	Oxidants	K1
	Etoposide	HB3	Δ Microscopy	×	×	×
	Starvation	K1					[23]
	Heat	3D7		Δ↑ TUNEL by fluorescence microscopy			[27]
	Increased parasite density	Dd2		Δ↑ TUNEL by flow cytometry and fluorescence microscopy	Δ↓ TMRE flow cytometry	Δ↑ protease mRNA and protein	[36]
Apoptosis/Autophagy	Chloroquine; S. nudum extracts	7G8	Δ Microscopy, electron microscopy	Δ↑ TUNEL by flow cytometry	Δ↓ DiOC6 Flow cytometry	×	[24]
Autophagy	Chloroquine; SNAP; Staurosporine	PSS1	Δ Electron microscopy	NO CHANGE TUNEL by flow cytometry	Δ↓ Rhodamine 123 Flow cytometry	NO CHANGE; VAD inhibitor	[37]
Necrosis	Chloroquine; Staurosporine; Heat	CSC-1	Δ Microscopy, electron microscopy	NO CHANGE Agarose gel with SYBR Green staining	Δ↓ DiOC6 Flow cytometry	Δ↓Caspase assay, Flow cytometry and fluorescence microscopy, VAD, LETD, LEHD, and AEVD inhibitors	[38]
Undefined	Chloroquine	Lili	×	NO CHANGE Agarose gel and Southern blotting	×		[12]
	Etoposide	F32	NO CHANGE Microscopy	NO CHANGE TUNEL by flow cytometry	NO CHANGE; DiOC6 flow cytometry
	Atovaquone				Δ↓ DiOC6 flow cytometry	×	[25]
	SNAP		Δ Microscopy	Δ↑ Smear, Agarose gel with ethidium bromide staining
	Artemisinin; Ceramide; Mefloquine	FCR3	NO CHANGE Electron microscopy	NO CHANGE TUNEL and agarose gels	×	NO CHANGE; Caspase 3 assay	[39]
	Staurosporine	3D7	×	Δ↑ TUNEL by flow cytometry and fluorescence microscopy	Δ↓ JC-1 Flow cytometry	Δ↑ Caspase assay, flow cytometry, and VAD substrate NO CHANGE VAD inhibitor	[34]