Table 1 The relation of transition metals to pyroptosis and ferroptosis. Please note that the protective factors and pathways are underlined
From: The interplay of transition metals in ferroptosis and pyroptosis
Transition metal | Pathways related to ferroptosis | Pathways related to pyroptosis |
|---|---|---|
Fe | - ROS generation (Fenton reaction) [138, 139] - LOX cofactor [8] - GSH-GPX4 ROS suppression [145] - NCOA4 ferritinophagy [157] - p53 [152] | - ROS-Tom20-Bax-Caspase-GSDME [45] - ROS-NLRP3-ASC-Caspase-1 [161] |
Zn | - ZIP-7 [178] - NRF2/HO-1/GPX4 defence pathway [179] - lipoxygenase [181] - MT antioxidative function [169] | - NLRP3-ASC-Caspase-1 [11, 183] - ZEB2 [184] - TRPC6-NLRP3-ASC-Caspase-1 [47] |
Se | - TRIT1 isopenthenylation of GPX4 Sec-tRNA [193] - TFAP2c [191] -Sp1 [195] -NFR2 (protective) [197] - Ebselen [198] | - GPX4 PI3K/AKT/PTEN [200] - GPX4-NLRP3 inhibition [201] - selenium deficiency ROS/NLRP3/IL-1β [204] - selenium deficiency TXRND3 dysregulation [205] - selenium deficiency-miR-1656-GPX4-NLRP3 [188] |
Cu | - autophagic GPX4 degradation [215] - mitochondria perturbation and loss of antioxidant capacity in copper depletion [216] - dysregulation of iron homeostasis [217] | - IRE1α/XBP1(ER stress)-NLRP3 [49] |
Mo | -Â catalytic generation of ROS [219] | - unclear - possibly PTEN/PI3K/AKT [224] or Nrf2-mediated antioxidant defence response inhibition [223] |
Co | - Fenton-like reaction [228] | - ROS-NLRP3-Casspase-1 [229] - GDSME-Caspase-3/8/9 activation [230] |
Ni | - dysregulation of iron homeostasis [234] - downregulation of GPX4, FTH1, NCOA4 (Mitochondria damage and ferroptosis involved in Ni-induced hepatotoxicity in mice) [234] | - in SelM KO mice Ni up regulates ASC, AIM2, NLRP3, Caspase-1, IL-18 and IL-1β [239] |
Pt | - cis-platin inactivates GPX and depletes GSH [239]. - cis-platin increases the expression of transferrin receptor and ferritin, which increases cellular iron levels [240] - activation of vitamin D receptor alleviates cis-platin induced ferroptosis [243] - cis-platin bound 4-carboxylphenylboronic acid scavenges GSH [249] | - cis-platin activates the MEG3-NLRP3-Caspase-1-GSDMD axis [51] - cis-platin induces the CAPN1/CAPN2-BAK/BAX-Caspase-9-Caspase-3-GSDME pathway [53] - Cis-platin inhibits Caspase-3-GSDMD pathway in non-cancerous cells [250] - Lobaplatin-Caspase-3-GSDME [56] - Lobaplatin-JNK-Bax-Cytochrome c-Caspase-3/9, Lobaplatin-cIAP1/2 [57] - Pt II complexes- cGAS-STING pathway [251] |
Cd | - dysregulation of iron homeostasis by HO-1 activation [256] - ER stress mediated ferritinophagy [257] - PERK-eIF2α-ATF4-CHOP pathway [46, 257] - inhibition of KEAP1-Nrf2/ARE pathway [263] - alteration of miR-34a-5p/Sirt1axis [280] | - ROS-NLRP3-Caspase-1 [58] - p38 MAPK- NF-κB p65-leading to elevation of proinflammatory cytokines [59] - IRE1α/XBP1(ER stress)-NLRP3 [269] |
Hg | - GPX4 downregulation [271] | - in LPS treatment Hg disrupts ROS production and inhibits the ASC pyroptosome and GDSMD cleavage |
Pb | - GPX4, SLC7a11, Tfrc, and Slc40a1 alterations [274] | - Pb increases NLRP3 expression and Caspase-1 cleavage [53] |
U | - increased iron levels and decrease in GPX activity [277] - gamma radiation alters the levels of TRFC, SLC3A2, FTH1, ACSL4, GPX4 [278] - gamma radiation itself generates ROS [279] | no data |