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Biomarker: Granzyme A

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Analyte:

Granzyme A

Platform:

Matrix:

Human Serum

Status:

Experienced Running

Sensitivity-LLOQ/ULOQ:

LLOQ: 1.66 pg/mL

Biological or Clinical Significance:

Granzyme A (GzmA) is the most abundant serine protease in killer cell cytotoxic granules. GzmA activates a novel programmed cell death pathway that begins in the mitochondrion, where cleavage of NDUFS3 in electron transport complex I disrupts mitochondrial metabolism and generates reactive oxygen species (ROS). ROS drives the endoplasmic reticulum-associated SET complex into the nucleus, where it activates single-stranded DNA damage. GzmA also targets other important nuclear proteins for degradation, including histones, the lamins that maintain the nuclear envelope, and several key DNA damage repair proteins (Ku70, PARP-1).

Cells that are resistant to the caspases or GzmB by overexpressing bcl-2 family anti-apoptotic proteins or caspase or GzmB protease inhibitors are sensitive to GzmA. By activating multiple cell death pathways, killer cells provide better protection against a variety of intracellular pathogens and tumors. GzmA also has proinflammatory activity; it activates pro-interleukin-1β and may also have other proinflammatory effects that remain to be elucidated.

References:

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