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Science: why do people die of heat? Chinese scientists uncover the key mechanism of heatstroke death

2022-05-07 11:25:32Chinese industry information station

In the context of global warming , Extreme high temperature weather is becoming more and more frequent all over the world , The threat of heat stroke is also rising . However , There is a key question that has never been answered : Why does high temperature cause these fatal symptoms involving multiple systems in the human body ?

In an article published in 《 science 》 In the latest study of , Professor Lv Ben from the Third Xiangya Hospital of Central South University Uncover the key mechanism of heat radiation death , It also provides a direction for the prevention and treatment of heat radiation disease .

In previous vertebrate research , Scientists have found that programmed cell death is regulated by two proteins : Mixed line kinase region like protein (MLKL), And punching holes in the cell membrane Gasdermin Family proteins ( for example Gasdermin D). Interestingly , These two kinds of proteins correspond to two different ways of cell death :MLKL When activated, it can lead to necrotic apoptosis ( That is, the way cells die in radiation sickness ), This is a process of cell self destruction activated by signals ; and Activate Gasdermin D Can cause cell death , This is the main way of cell death triggered by pathogen infection .

about Gasdermin D, Previous studies have found that this protein plays a key role in infection induced sepsis : Its over activation can lead to disseminated intravascular coagulation and multiple organ failure . you 're right , These symptoms are also typical of heat stroke .

This connection inspired Professor Lu Ben's team : For critically ill patients with very similar symptoms , Both involve programmed cell death , and Gasdermin D The overactivation of leads to the symptoms of sepsis , So whether the similar symptoms of heat stroke are similar to MLKL About ?

MLKL The activation of is affected by Receptor interacting protein kinase 3(RIPK3) passageway Regulation , therefore , The team tried to test it in mice RIPK3 Channel and MLKL Role in heat stroke . Knock out RIPK3 Post gene , In lethal heat 、 Mice in high humidity environment almost no longer have symptoms related to heat radiation disease ; And knocking out MLKL In genetically modified mice , Most of them survived . This series of experiments shows that , Programmed cell necrosis in radiation sickness is mainly caused by RIPK3 access , as well as RIPK3 Phosphorylated substrate MLKL Controlled by .

Next , The research team followed the vine and felt the melon , A challenge to the next question : How does heat stress affect RIPK3 The tunnel ? They targeted Z-DNA Binding proteins -1(ZBP1): Knock out in mouse experiments ZBP1 Post gene , It can also avoid the symptoms of heat stroke .

The study found that ,ZBP1 There are heat shock factors in the promoter region of 1(HSF1) The binding site of , therefore Heat stress can be through HSF1 increase ZBP1 The expression of , also ZBP1 The activation mechanism of is independent of nucleic acid recognition . And then ,ZBP1 Further induce RIPK3 Pathway activation , Finally, it leads to programmed cell necrosis .

It is worth mentioning that , Previous studies have found that ZBP1 Role in antiviral infection , This study reveals a second function of these proteins in cells : Induce programmed cell necrosis .

When we will ZBP1 Put the two functions together , Maybe we can understand the reason why this mechanism appears . Infection often leads to high fever , Excessive body temperature may be activated by ZBP1 Promote the removal of pathogens 、 Promote inflammatory response . However , Continuous exposure to ambient heat will over activate this cell necrosis process , Cause a variety of fatal symptoms .

This mechanism evolved for survival , But it is putting more people in danger . When people gradually uncover the molecular mechanism of heat stroke , Those at high risk may usher in safer 、 Effective prevention and control strategies .

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