Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis

Lin, Lin; Zhang, Mu-xin; Zhang, Lei; Zhang, Dan; Li, Chao; Li, Yunlun

doi:10.3389/fcell.2021.809955

Cited by 62 publications

(58 citation statements)

References 315 publications

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“…Different types of RCD occasionally share the same upstream molecules; accordingly, crosstalk between RCD pathways is inevitable. Ferroptosis is an iron-dependent form of RCD, and differs from apoptosis by excessive lipid peroxidation, lack of glutathione, and inactivation of caspase-3 (50,51). However, a recent study demonstrated that the ER stress-mediated CHOP-PUMA pathway was associated with the interaction between apoptosis and ferroptosis (52).…”

Section: Discussionmentioning

confidence: 99%

Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells

Dong

Liang

et al. 2022

Int J Oncol

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Leukemia is a fatal hematopoietic disorder with a poor prognosis. Drug resistance is inevitable after the long-term use of chemotherapeutic agents. Liproxstatin-1, commonly known as a ferroptosis inhibitor, has never been reported to have anticancer effects. In the present study, the antileukemic role of liproxstatin-1 in K562 leukemia cells was investigated. Liproxstatin-1 inhibited K562 cell proliferation in a dose-and time-dependent manner. RNA sequencing revealed several pathways that were affected by liproxstatin-1, such as the G1/S transition of the mitotic cell cycle and extrinsic or intrinsic apoptotic signaling pathways. The results of flow cytometry indicated that liproxstatin-1 arrests the cell cycle at the G1 phase, and even at the G2/M phase. p21 WAF1/CIP1 , a cyclin-dependent kinase inhibitor, was upregulated. It was also determined that liproxstatin-1 induced BAX and TNF-α expression, which was accompanied by cleavage of caspase-3 and PARP. The caspase-3-specific inhibitor z-DEVD-FMK rescued some of the apoptotic cells. Interestingly, K562 cells were characterized by swelling and plasma membrane rupture when treated with a high concentration of liproxstatin-1, which was inconsistent with the typical apoptotic appearance. Thus, it was hypothesized that apoptosis-mediated pyroptosis occurs during liproxstatin-1-induced cell death. The expression of the hallmark of pyroptosis, the cleaved N-terminal GSDME, increased. Additionally, it was observed that endoplasmic reticulum stress and autophagy were involved in liproxstatin-1-induced cell death. Collectively, liproxstatin-1 induced cell cycle arrest, apoptosis, and caspase-3/GSDME-dependent secondary pyroptosis in K562 leukemia cells, which provides new hope for the treatment of leukemia.

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Section: Discussionmentioning

confidence: 99%

Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells

Dong

Liang

et al. 2022

Int J Oncol

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“…Apoptosis is characteristic by DNA fragmentation, destruction of the nuclear proteins and cytoskeleton, crosslinking of proteins, and the formation of apoptotic bodies [ 60 ]. Pyroptosis leads to cell swelling, pore formation, membrane rupture, and massive leakage of cytoplasmic components [ 61 ]. The links and mutual regulatory mechanisms between ferroptosis and other models of cell death are discussed below ( Figure 2 ).…”

Section: Ferroptosis and Other Cell Models Of Death After Tbimentioning

confidence: 99%

Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

Pang

Zheng

Ren

et al. 2022

Oxidative Medicine and Cellular Longevity

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Traumatic brain injury (TBI) is a serious health issue with a high incidence, high morbidity, and high mortality that poses a large burden on society. Further understanding of the pathophysiology and cell death models induced by TBI may support targeted therapies for TBI patients. Ferroptosis, a model of programmed cell death first defined in 2012, is characterized by iron dyshomeostasis, lipid peroxidation, and glutathione (GSH) depletion. Ferroptosis is distinct from apoptosis, autophagy, pyroptosis, and necroptosis and has been shown to play a role in secondary brain injury and worsen long-term outcomes after TBI. This review systematically describes (1) the regulatory pathways of ferroptosis after TBI, (2) the neurobiological links between ferroptosis and other cell death models, and (3) potential therapies targeting ferroptosis for TBI patients.

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“…Under homeostatic conditions, these processes are used to remove damaged, infected, or mutated cells. However, in the context of ASCVD, loss of control over these processes can promote disease [ 29 ]. A highly regulated process for the clearance of dead cells, termed “efferocytosis,”, is another important aspect of inflammatory resolution and many studies show that enhancing efferocytosis can reduce plaque sizes in mouse models [ 30 ].…”

Section: Inflammation In Cardiovascular Diseasementioning

confidence: 99%

Immune Cell Activation in Obesity and Cardiovascular Disease

et al. 2022

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Purpose of Review In this review, we focus on immune cell activation in obesity and cardiovascular disease, highlighting specific immune cell microenvironments present in individuals with atherosclerosis, non-ischemic heart disease, hypertension, and infectious diseases. Recent Findings Obesity and cardiovascular disease are intimately linked and often characterized by inflammation and a cluster of metabolic complications. Compelling evidence from single-cell analysis suggests that obese adipose tissue is inflammatory and infiltrated by almost all immune cell populations. How this inflammatory tissue state contributes to more systemic conditions such as cardiovascular and infectious disease is less well understood. However, current research suggests that changes in the adipose tissue immune environment impact an individual’s ability to combat illnesses such as influenza and SARS-CoV2 . Summary Obesity is becoming increasingly prevalent globally and is often associated with type 2 diabetes and heart disease. An increased inflammatory state is a major contributor to this association. Widespread chronic inflammation in these disease states is accompanied by an increase in both innate and adaptive immune cell activation. Acutely, these immune cell changes are beneficial as they sustain homeostasis as inflammation increases. However, persistent inflammation subsequently damages tissues and organs throughout the body. Future studies aimed at understanding the unique immune cell populations in each tissue compartment impacted by obesity may hold potential for therapeutic applications.

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Autophagy, Pyroptosis, and Ferroptosis: New Regulatory Mechanisms for Atherosclerosis

Cited by 62 publications

References 315 publications

Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells

Liproxstatin‑1 induces cell cycle arrest, apoptosis, and caspase‑3/GSDME‑dependent secondary pyroptosis in K562 cells

Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury

Immune Cell Activation in Obesity and Cardiovascular Disease

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