Abstract
Hibernating 13-lined ground squirrels are characterized by tolerance of severe hypothermia and hypoperfusion during torpor, followed by periodic warm reperfusion during IBA, conditions which are lethal to nonhibernating mammals. The aim of the present study was to determine whether protection from apoptosis was specific to torpor arousal cycles during hibernation or will also apply to cisplatin treatment on squirrel renal tubular cells (RTECs) that were procured during hibernation. Squirrel and mouse RTECs were treated with cisplatin, a potent inducer of RTEC apoptosis. Squirrel RTECs subjected to cisplatin had significantly less apoptosis, no cleaved caspase-3, and increased XIAP, pAkt, and pBAD versus mouse RTECs. To determine whether XIAP and Akt1 are necessary for RTEC protection against cisplatin induced apoptotic cell death, gene expression of Akt1 or XIAP was silenced in squirrel RTECs. Squirrel RTECs deficient in Akt1 and XIAP had increased apoptosis and cleaved caspase-3 when treated with cisplatin. Our results thus demonstrates that 13-lined ground squirrel RTECs possess intrinsic intracellular mechanisms by which they protect themselves from apoptotic cell death. Cisplatin induced acute kidney injury (AKI) may be avoided in cancer patients by employing mechanisms used by squirrel RTECs to protect against cisplatin induced tubular cell apoptosis.
Highlights
Torpor (LT) Core body temperature (CBT) = 4°C HR = 3–5 RR = 4–6 torpor arousal or was a nonspecific response that would occur in response to any apoptotic stimuli
To determine whether the protection of ground squirrel Renal tubular cells acute kidney injury (AKI) (RTECs) from caspase-3 activation and apoptotic cell death during cisplatin treatment was associated with an increase in antiapoptotic proteins, we examined the expression of X-linked inhibitor of apoptosis protein (XIAP), pAkt (Ser473), and pBAD (Ser136) in RTECS treated with cisplatin
We sought to discover whether 13-lined ground squirrel RTECs are protected from apoptotic cell death during treatment with cisplatin, a potent inducer of apoptosis [8]
Summary
Torpor (LT) CBT = 4°C HR = 3–5 (beats/min) RR = 4–6 (breaths/min) torpor arousal or was a nonspecific response that would occur in response to any apoptotic stimuli. We procured cortical renal tubular cells (RTECs) from hibernating 13-lined ground squirrel kidneys and subjected them to treatment with the chemotherapeutic agent cisplatin, a potent inducer of renal tubular cell death [8]. We hypothesized that the ground squirrel RTECS demonstrated intrinsic protective mechanisms that would protect them from apoptosis during treatment with cisplatin in a setting distinct from torpor arousal
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