Clinical and molecular hepatology · 2025
Novel near-infrared probe for monitoring lipid peroxidation-mediated viscosity change in ferroptotic hepatocytes.
СтатьяНазвание и аннотация: Перевод в очереди
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Pham Le Bich Hang, Kim Taeeung, Kim Seoyoung, Kim Yun Seok, Kim Jiyeon, Kim Kyeongseon, Lim Hyeonwoo, Shim Wan Seob, Kim Byoungmo, Yoo So-Yeol, Lee Jae-Young, Choi Murim, Kim Won, Kang Keon Wook, Lee Jeeyeon
Аннотация
BACKGROUND/AIMS: Ferroptosis, recently emerged as a new cell death modality characterized by iron-dependent peroxidation of lipids, has been explored in various diseases. However, detection of ferroptosis, particularly in chronic liver disease models, is hampered by the lack of universal ferroptosis markers and limited number of fluorescence sensors for in vivo ferroptosis.
METHODS: In this study, we developed TTM-4 as a highly sensitive near-infrared (NIR) fluorescent probe to detect ferroptosis.
RESULTS: TTM-4 exhibited turn-on fluorescence upon viscosity change, enabling visualization of lipid peroxidation (LPO) in ferroptotic hepatocytes and liver tissue samples with greater sensitivity than BODIPY 581/591 C11. Timelapse live-cell imaging of erastin-treated cells revealed real-time LPO dynamics involving cytosolic lipid droplets (cLDs), endoplasmic reticulum, and nuclear LDs in a chronological order. Further gene expression analysis of 216 liver tissue samples from the NCBI GEO database showed a significant increase in CIDEC concurrent with TTM-4 fluorescence during progression to metabolic dysfunction-associated steatotic hepatitis (MASH). TTM-4, with its low toxicity and turn-on NIR emission during ferroptosis, also enabled in vivo visualization of ferroptosis in liver injury and metabolic dysfunction-associated steatotic liver disease (MASLD) models.
CONCLUSIONS: Our findings suggest that TTM-4 enables monitoring of ferroptosis in MASLD and would aid in early MASH diagnosis.
METHODS: In this study, we developed TTM-4 as a highly sensitive near-infrared (NIR) fluorescent probe to detect ferroptosis.
RESULTS: TTM-4 exhibited turn-on fluorescence upon viscosity change, enabling visualization of lipid peroxidation (LPO) in ferroptotic hepatocytes and liver tissue samples with greater sensitivity than BODIPY 581/591 C11. Timelapse live-cell imaging of erastin-treated cells revealed real-time LPO dynamics involving cytosolic lipid droplets (cLDs), endoplasmic reticulum, and nuclear LDs in a chronological order. Further gene expression analysis of 216 liver tissue samples from the NCBI GEO database showed a significant increase in CIDEC concurrent with TTM-4 fluorescence during progression to metabolic dysfunction-associated steatotic hepatitis (MASH). TTM-4, with its low toxicity and turn-on NIR emission during ferroptosis, also enabled in vivo visualization of ferroptosis in liver injury and metabolic dysfunction-associated steatotic liver disease (MASLD) models.
CONCLUSIONS: Our findings suggest that TTM-4 enables monitoring of ferroptosis in MASLD and would aid in early MASH diagnosis.